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Syed AA, Adam S, Miller CA, Alkhaffaf B. Obesity Management for Patients with Coronary Artery Disease and Heart Failure. Heart Fail Clin 2025; 21:257-271. [PMID: 40107803 DOI: 10.1016/j.hfc.2024.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/22/2025]
Abstract
Obesity is causally linked to heart disease directly by triggering various adverse pathophysiological changes and indirectly through convergent risk factors such as type 2 diabetes, hypertension, dyslipidemia, and sleep disorder. Weight reduction is an important intervention for obesity-related cardiomyopathy, and antiobesity medications that target both obesity and heart failure (HF), particularly sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists, have a role in treatment. Bariatric surgery offers a viable treatment option for patients with severe obesity associated with coronary artery disease and HF but requires careful patient selection, preoperative optimization, choice of procedure, and postoperative management to minimize risks.
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Affiliation(s)
- Akheel A Syed
- Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK; Department of Diabetes, Endocrinology & Obesity Medicine, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK.
| | - Safwaan Adam
- Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK; Department of Diabetes & Endocrinology, The Christie NHS Foundation Trust, Wilmslow Road, Manchester, M20 4BX, UK
| | - Christopher A Miller
- Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK; BHF (British Heart Foundation) Manchester Centre for Heart and Lung Magnetic Resonance Research, Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Wythenshawe Hospital, Manchester M23 9LT, UK
| | - Bilal Alkhaffaf
- Faculty of Biology, Medicine and Health, University of Manchester, Oxford Road, Manchester M13 9PL, UK; Department of Oesophago-Gastric & Bariatric Surgery, Salford Royal Hospital, Northern Care Alliance NHS Foundation Trust, Stott Lane, Salford M6 8HD, UK
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Ebong IA, Wilson M, Michos ED, Appiah D, Schreiner PJ, Racette SB, Allison M, Watson K, Bertoni A. Menopausal age, adipokines, and heart failure incidence in postmenopausal women of the Multi-Ethnic Study of Atherosclerosis. Menopause 2025; 32:72-80. [PMID: 39626171 DOI: 10.1097/gme.0000000000002456] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2024]
Abstract
OBJECTIVE The mechanisms through which menopausal age influences heart failure (HF) development are controversial. Adiposity increases after menopause and could affect HF risk by influencing serum adipokine secretion. We investigated the associations of early menopause, and serum adipokines with incident HF in postmenopausal women. METHODS We included 746 postmenopausal women from the Multi-Ethnic Study of Atherosclerosis who reported their menopausal age and had data on adipokines and incident HF at the end of follow-up. Multivariable Cox proportional hazards models were used for analysis. RESULTS The mean age was 65.1 years. Over a median follow-up period of 17.8 years, 45 HF events occurred. After adjusting for waist circumference, other cardiovascular disease risk factors and myocardial infarction, the hazard ratios (95% confidence intervals) of incident HF attributable to early menopause were 4.50 (1.41-14.3), 4.64 (1.46-14.7), and 5.16 (1.59-16.7) in models that additionally included adiponectin, leptin, and resistin, respectively. In adjusted analyses, adiponectin was independently associated with incident HF 2.20 (1.35-3.57), while leptin and resistin were not. The interaction terms of early menopause with adiponectin, leptin, and resistin for incident HF were not significant ( Pint = 0.08-0.82). CONCLUSIONS Early menopause was significantly associated with incident HF. This association did not differ by serum adipokine levels. Only adiponectin was independently associated with incident HF in postmenopausal women when waist circumference, body mass index, and waist-hip ratio were used as the adiposity metric.
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Affiliation(s)
| | | | - Erin D Michos
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Duke Appiah
- Department of Public Health, Texas Tech University Health Sciences Center, Lubbock, TX
| | | | - Susan B Racette
- College of Health Solutions, Arizona State University, Phoenix, AZ
| | - Matthew Allison
- Department of Family Medicine, University of California San Diego, San Diego, CA
| | - Karol Watson
- Division of Cardiovascular Medicine, University of California Los Angeles, Los Angeles, CA
| | - Alain Bertoni
- Division of Public Health Sciences, Wake Forest University School of Medicine, Winston Salem, NC
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Ma H, Wang X, Heianza Y, Manson JE, Qi L. Proteomic Signature of BMI and Risk of Cardiovascular Disease. Clin Chem 2024; 70:1474-1484. [PMID: 39392242 DOI: 10.1093/clinchem/hvae149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2024] [Accepted: 08/21/2024] [Indexed: 10/12/2024]
Abstract
BACKGROUND Obesity, defined by body mass index (BMI) alone, is a metabolically heterogeneous disorder with distinct cardiovascular manifestations across individuals. This study aimed to investigate the associations of a proteomic signature of BMI with risk of major subtypes of cardiovascular disease (CVD). METHODS A total of 40 089 participants from UK Biobank, free of CVD at baseline, had complete data on proteomic data measured by the Olink assay. A BMI-proteomic score (pro-BMI score) was calculated from 67 pre-identified plasma proteins associated with BMI. RESULTS A higher pro-BMI score was significantly associated with higher risks of ischemic heart disease (IHD) and heart failure (HF), but not with risk of stroke. Comparing the highest with the lowest quartiles, the adjusted hazard ratio (HR) for IHD was 1.49 (95% CI, 1.32-1.67) (P-trend < 0.001), and the adjusted HR for HF was 1.52 (95% CI, 1.25-1.85) (P-trend < 0.001). Further analyses showed that the association of pro-BMI score with HF risk was largely driven by the actual BMI, whereas the association of the pro-BMI score with IHD risk was independent of actual BMI and waist-to-hip ratio (WHR). The association between pro-BMI score and IHD risk appeared to be stronger in the normal BMI group than other BMI groups (P-interaction = 0.004) and stronger in the normal WHR group than the high WHR group (P-interaction = 0.049). CONCLUSIONS Higher pro-BMI score is significantly associated with higher IHD risk, independent of actual BMI levels. Our findings suggest that plasma proteins hold promise as complementary markers for diagnosing obesity and may facilitate personalized interventions.
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Affiliation(s)
- Hao Ma
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
| | - Xuan Wang
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
| | - Yoriko Heianza
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
| | - JoAnn E Manson
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, United States
- Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, United States
| | - Lu Qi
- Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, New Orleans, LA, United States
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, United States
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Theodorakis N, Kreouzi M, Hitas C, Anagnostou D, Nikolaou M. Adipokines and Cardiometabolic Heart Failure with Preserved Ejection Fraction: A State-of-the-Art Review. Diagnostics (Basel) 2024; 14:2677. [PMID: 39682585 PMCID: PMC11640255 DOI: 10.3390/diagnostics14232677] [Citation(s) in RCA: 14] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2024] [Revised: 11/25/2024] [Accepted: 11/26/2024] [Indexed: 12/18/2024] Open
Abstract
BACKGROUND Cardiometabolic heart failure with preserved ejection fraction (HFpEF) is largely driven by obesity-related factors, including adipokines and bioactive peptides primarily secreted by the adipose tissue, such as leptin, adiponectin, and resistin. These molecules link metabolic dysregulation to cardiovascular dysfunction, influencing HFpEF progression and patient outcomes Methods: A comprehensive literature search was conducted in PubMed up to 20 November 2024, using keywords and MeSH terms, such as "HFpEF", "adipokines", "leptin", "adiponectin", and "resistin", yielding 723 results. Boolean operators refined the search, and reference lists of key studies were reviewed. After screening for duplicates and irrelevant studies, 103 articles were included, providing data on adipokines' roles in HFpEF pathophysiology, biomarkers, and therapeutic implications. RESULTS Both preclinical and clinical studies have demonstrated that adipokines play a role in modulating cardiovascular function, thereby contributing to the development of cardiometabolic HFpEF. Leptin promotes myocardial hypertrophy, fibrosis, endothelial dysfunction, and inflammation, though contradictory evidence suggests potential cardioprotective roles in subgroups like obese African American women. Adiponectin generally offers protective effects but presents a paradox, where elevated levels may correlate with worse outcomes, which may reflect either a compensatory response to cardiac dysfunction or a maladaptive state characterized by adiponectin resistance. Resistin is associated with increased cardiovascular risk through pro-inflammatory and pro-fibrotic effects, though its role in HFpEF requires further clarification. Other adipokines, like retinol-binding protein 4 and omentin-1, have emerged as potential contributors. Despite growing insights, clinical translation remains limited, underscoring a significant gap between experimental evidence and therapeutic application. CONCLUSIONS Future research should focus on targeted interventions that modulate adipokine pathways to potentially improve HFpEF outcomes. Innovative treatment strategies addressing underlying metabolic disturbances and adipokine dysregulation are essential for advancing the management of this challenging condition.
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Affiliation(s)
- Nikolaos Theodorakis
- School of Medicine, National and Kapodistrian University of Athens, 75 Mikras Asias, 11527 Athens, Greece;
- Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, 14 25is Martiou Str., 15127 Melissia, Greece; (C.H.); (D.A.)
| | - Magdalini Kreouzi
- Department of Internal Medicine, Sismanogleio-Amalia Fleming General Hospital, 14 25is Martiou Str., 15127 Melissia, Greece;
| | - Christos Hitas
- Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, 14 25is Martiou Str., 15127 Melissia, Greece; (C.H.); (D.A.)
| | - Dimitrios Anagnostou
- Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, 14 25is Martiou Str., 15127 Melissia, Greece; (C.H.); (D.A.)
| | - Maria Nikolaou
- Department of Cardiology & Heart Failure Outpatient Clinic, Sismanogleio-Amalia Fleming General Hospital, 14 25is Martiou Str., 15127 Melissia, Greece; (C.H.); (D.A.)
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Lima GB, Figueiredo N, Kattah FM, Oliveira ES, Horst MA, Dâmaso AR, Oyama LM, Whitton RGM, de Souza GIMH, Lima GC, Mota JF, Campos RMS, Corgosinho FC. Serum Fatty Acids and Inflammatory Patterns in Severe Obesity: A Preliminary Investigation in Women. Biomedicines 2024; 12:2248. [PMID: 39457561 PMCID: PMC11505423 DOI: 10.3390/biomedicines12102248] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2024] [Revised: 09/29/2024] [Accepted: 09/30/2024] [Indexed: 10/28/2024] Open
Abstract
Background: Inflammation plays a central role in many chronic diseases that characterize modern society. Leptin/adiponectin and adiponectin/leptin ratios have been recognized as notable markers of dysfunctional adipose tissue and, consequently, an inflammatory state. Methods: Blood samples were collected from 41 adult volunteers (40.2 ± 8.3 years) diagnosed with severe obesity (BMI 46.99; 42.98-51.91 kg/m2). The adipokines were quantified using an enzyme-linked immunosorbent assay, while the serum fatty acid analysis was conducted using chromatography. Results: The results unveiled a positive correlation between the leptin/adiponectin ratio and the 20:3n6 fatty acid (r = 0.52, p = 0.001), as well as a similar positive correlation between the adiponectin/leptin ratio and the 22:6n3 fatty acid (r = 0.74, p = 0.001). In the regression analysis, the 22:6n3 fatty acid predicted the adiponectin/leptin ratio (β = 0.76, p < 0.001), whereas C20:3 n-6 was a predictor for inflammatory markers (β = 4.84, p < 0.001). Conclusions: In conclusion, the 22:6n3 fatty acid was demonstrated to be a predictive factor for the adiponectin/leptin ratio and C20:3 n-6 was a predictor for inflammatory markers. This discovery, novel within this population, can help develop new intervention strategies aimed at controlling the inflammatory status in individuals classified as having severe obesity.
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Affiliation(s)
- Gislene B. Lima
- Postgraduate Program in Nutrition and Health, Faculty of Nutrition, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil; (F.M.K.); (E.S.O.); (M.A.H.); (G.C.L.); (J.F.M.); (F.C.C.)
| | - Nayra Figueiredo
- Postgraduate Program in Health Sciences, Faculty of Medicine, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil;
| | - Fabiana M. Kattah
- Postgraduate Program in Nutrition and Health, Faculty of Nutrition, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil; (F.M.K.); (E.S.O.); (M.A.H.); (G.C.L.); (J.F.M.); (F.C.C.)
| | - Emilly S. Oliveira
- Postgraduate Program in Nutrition and Health, Faculty of Nutrition, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil; (F.M.K.); (E.S.O.); (M.A.H.); (G.C.L.); (J.F.M.); (F.C.C.)
| | - Maria A. Horst
- Postgraduate Program in Nutrition and Health, Faculty of Nutrition, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil; (F.M.K.); (E.S.O.); (M.A.H.); (G.C.L.); (J.F.M.); (F.C.C.)
| | - Ana R. Dâmaso
- Interdisciplinary Postgraduate Program in Health Sciences, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil; (A.R.D.); (L.M.O.); (G.I.M.H.d.S.); (R.M.S.C.)
| | - Lila M. Oyama
- Interdisciplinary Postgraduate Program in Health Sciences, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil; (A.R.D.); (L.M.O.); (G.I.M.H.d.S.); (R.M.S.C.)
| | - Renata G. M. Whitton
- Institute of Biosciences, Federal University of São Paulo (USP), São Paulo 05508-900, Brazil;
| | - Gabriel I. M. H. de Souza
- Interdisciplinary Postgraduate Program in Health Sciences, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil; (A.R.D.); (L.M.O.); (G.I.M.H.d.S.); (R.M.S.C.)
| | - Glaucia C. Lima
- Postgraduate Program in Nutrition and Health, Faculty of Nutrition, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil; (F.M.K.); (E.S.O.); (M.A.H.); (G.C.L.); (J.F.M.); (F.C.C.)
| | - João F. Mota
- Postgraduate Program in Nutrition and Health, Faculty of Nutrition, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil; (F.M.K.); (E.S.O.); (M.A.H.); (G.C.L.); (J.F.M.); (F.C.C.)
- Postgraduate Program in Health Sciences, Faculty of Medicine, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil;
| | - Raquel M. S. Campos
- Interdisciplinary Postgraduate Program in Health Sciences, Federal University of São Paulo (UNIFESP), São Paulo 04039-032, Brazil; (A.R.D.); (L.M.O.); (G.I.M.H.d.S.); (R.M.S.C.)
| | - Flávia C. Corgosinho
- Postgraduate Program in Nutrition and Health, Faculty of Nutrition, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil; (F.M.K.); (E.S.O.); (M.A.H.); (G.C.L.); (J.F.M.); (F.C.C.)
- Postgraduate Program in Health Sciences, Faculty of Medicine, Federal University of Goiás (UFG), Goiânia 74690-900, Brazil;
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Quispe R, Sweeney T, Martin SS, Jones SR, Allison MA, Budoff MJ, Ndumele CE, Elshazly MB, Michos ED. Associations of Adipokine Levels With Levels of Remnant Cholesterol: The Multi-Ethnic Study of Atherosclerosis. J Am Heart Assoc 2024; 13:e030548. [PMID: 39248264 PMCID: PMC11935629 DOI: 10.1161/jaha.123.030548] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 03/06/2024] [Indexed: 09/10/2024]
Abstract
BACKGROUND The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. METHODS AND RESULTS We studied 1791 MESA (Multi-Ethnic Study of Atherosclerosis) participants who took part in an ancillary study on body composition with adipokine levels measured (leptin, adiponectin, and resistin) at either visit 2 or visit 3. RC was calculated as non-high-density lipoprotein cholesterol minus low-density lipoprotein cholesterol, measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed-effects models were used to assess the cross-sectional and longitudinal associations between adipokines and log-transformed levels of RC. Mean±SD age was 64.5±9.6 years; mean±SD body mass index was 29.9±5.0 kg/m2; and 52.0% were women. In fully adjusted cross-sectional models that included body mass index, diabetes, low-density lipoprotein cholesterol, and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.6% (95% CI, 12.2-16.9) lower RC. With each 1-unit increment in leptin and resistin, there was 4.8% (95% CI, 2.7-7.0) and 4.0% (95% CI, 0.2-8.1) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5 (interquartile range, 4-8) years. CONCLUSIONS Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for body mass index and low-density lipoprotein cholesterol.
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Affiliation(s)
- Renato Quispe
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Ty Sweeney
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Seth S. Martin
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Steven R. Jones
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Matthew A. Allison
- Department of Family MedicineUniversity of California San DiegoSan DiegoCA
| | | | - Chiadi E. Ndumele
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
| | - Mohamed B. Elshazly
- Department of Cardiovascular MedicineHeart and Vascular Institute, Cleveland ClinicClevelandOH
| | - Erin D. Michos
- Ciccarone Center for the Prevention of Cardiovascular DiseaseJohns Hopkins University School of MedicineBaltimoreMD
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Myasoedova VA, Bertolini F, Valerio V, Moschetta D, Massaiu I, Rusconi V, De Giorgi D, Ciccarelli M, Parisi V, Poggio P. The Role of Adiponectin and Leptin in Fibro-Calcific Aortic Valve Disease: A Systematic Review and Meta-Analysis. Biomedicines 2024; 12:1977. [PMID: 39335491 PMCID: PMC11428218 DOI: 10.3390/biomedicines12091977] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/12/2024] [Accepted: 08/13/2024] [Indexed: 09/30/2024] Open
Abstract
BACKGROUND Fibro-calcific aortic valve disease (FCAVD) is a progressive disorder characterized by the thickening and calcification of the aortic valve, eventually leading to aortic stenosis. Adiponectin and leptin, known for their anti-inflammatory and proinflammatory properties, respectively, have been implicated in cardiovascular diseases, but their associations with FCAVD are controversial. This meta-analysis aims to evaluate the relationships between adiponectin and leptin levels and FCAVD, particularly in patients with severe aortic stenosis (AS). METHODS A systematic search was conducted across the PubMed, Scopus, and Web of Science databases to identify studies on adiponectin and leptin levels in FCAVD. The methodological quality of each study was assessed using the Newcastle-Ottawa Scale. Standardized mean differences (SMDs) and 95% confidence intervals (CIs) were calculated, and publication bias was evaluated using Egger's test and funnel plots. RESULTS Out of 191 articles identified, 10 studies involving 2360 patients (989 with FCAVD and 1371 controls) were included. The analysis suggested trends in the associations of lower adiponectin levels (SMD = -0.143, 95% CI: -0.344, 0.057, p = 0.161) and higher leptin levels (SMD = 0.175, 95% CI: -0.045, 0.395, p = 0.119) with FCAVD. The association remained a trend for low adiponectin but showed a significant correlation with high leptin in severe AS patients (SMD = 0.29, 95% CI: 0.036, 0.543, p = 0.025). CONCLUSION This meta-analysis indicates a potential association between elevated leptin levels and severe aortic stenosis, while the relationship with adiponectin levels remains inconclusive. These findings highlight the need for further and dedicated research to clarify the roles of these adipokines in the pathogenesis of FCAVD and their potential roles as biomarkers for disease progression.
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Affiliation(s)
| | | | | | | | | | | | | | - Michele Ciccarelli
- Department of Medicine, Surgery and Dentistry, University of Salerno, 84084 Fisciano, Italy
| | - Valentina Parisi
- Department of Translational Medical Sciences, Federico II University, 80138 Naples, Italy
| | - Paolo Poggio
- Centro Cardiologico Monzino IRCCS, 20138 Milan, Italy
- Department of Biomedical, Surgical and Dental Sciences, University of Milan, 20122 Milan, Italy
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Habib S. Metabolic dysfunction-associated steatotic liver disease heterogeneity: Need of subtyping. World J Gastrointest Pathophysiol 2024; 15:92791. [PMID: 38845820 PMCID: PMC11151879 DOI: 10.4291/wjgp.v15.i2.92791] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Revised: 04/04/2024] [Accepted: 04/24/2024] [Indexed: 05/23/2024] Open
Abstract
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a widespread global disease with significant health burden. Unhealthy lifestyle, obesity, diabetes mellitus (DM), insulin resistance, and genetics have been implicated in the pathogenesis of MASLD. A significant degree of heterogeneity exists among each of above-mentioned risk factors. Heterogeneity of these risk factors translates into the heterogeneity of MASLD. On the other hand, MASLD can itself lead to insulin resistance and DM. Such heterogeneity makes it difficult to assess the natural course of an individual with MASLD in clinical practice. At present MASLD is considered as one disease despite the variability of etiopathogenic processes, and we lack the consensus definitions of unique subtypes of MASLD. In this review, pathogenic processes of MASLD are discussed and a need of subtyping is recommended.
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Affiliation(s)
- Shahid Habib
- Department of Hepatology, Liver Institute PLLC, Tucson, AZ 85716, United States
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9
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Ramirez MF, Lau ES, Parekh JK, Pan AS, Owunna N, Wang D, McNeill JN, Malhotra R, Nayor M, Lewis GD, Ho JE. Obesity-Related Biomarkers Are Associated With Exercise Intolerance and HFpEF. Circ Heart Fail 2023; 16:e010618. [PMID: 37703087 PMCID: PMC10698557 DOI: 10.1161/circheartfailure.123.010618] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2023] [Accepted: 08/13/2023] [Indexed: 09/14/2023]
Abstract
BACKGROUND Obesity and adiposity are associated with an increased risk of heart failure with preserved ejection fraction (HFpEF); yet, specific underlying mechanisms remain unclear. We sought to examine the association of obesity-related biomarkers including adipokines (leptin, resistin, adiponectin), inflammatory markers (CRP [C-reactive protein], IL-6 [interleukin-6]), and insulin resistance (HOMA-IR) with HFpEF status, exercise capacity, and cardiovascular outcomes. METHODS We studied 509 consecutive patients with left ventricular ejection fraction ≥50% and chronic dyspnea, who underwent clinically indicated cardiopulmonary exercise test with invasive hemodynamic monitoring between 2006 and 2017. We defined HFpEF based on the presence of elevated left ventricular filling pressures at rest or during exercise. Fasting blood samples collected at the time of the cardiopulmonary exercise test were used to assay obesity-related biomarkers. We examined the association of log-transformed biomarkers with HFpEF status and exercise traits using multivariable-adjusted logistic regression models. RESULTS We observed associations of obesity-related biomarkers with measures of impaired exercise capacity including peak VO2 (P≤0.002 for all biomarkers). The largest effect size was seen with leptin, where a 1-SD higher leptin was associated with a 2.35 mL/kg per min lower peak VO2 (β, -2.35±0.19; P<0.001). In addition, specific biomarkers were associated with distinct measures of exercise reserve including blood pressure (homeostatic model assessment of insulin resistance, leptin, adiponectin; P≤0.002 for all), and chronotropic response (CRP, IL-6, homeostatic model assessment of insulin resistance, leptin, and resistin; P<0.05 for all). Our findings suggest that among the obesity-related biomarkers studied, higher levels of leptin and CRP are independently associated with increased odds of HFpEF, with odds ratios of 1.36 (95% CI, 1.09-1.70) and 1.25 (95% CI, 1.03-1.52), respectively. CONCLUSIONS Specific obesity-related pathways including inflammation, adipokine signaling, and insulin resistance may underlie the association of obesity with HFpEF and exercise intolerance.
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Affiliation(s)
- Mariana F. Ramirez
- Cardiovascular Institute and Division of Cardiology,
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Emily S. Lau
- Division of Cardiology, Department of Medicine,
Massachusetts General Hospital, Boston, MA, USA
| | - Juhi K. Parekh
- Cardiovascular Institute and Division of Cardiology,
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Abigail S. Pan
- Cardiovascular Institute and Division of Cardiology,
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Ndidi Owunna
- Cardiovascular Institute and Division of Cardiology,
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
| | - Dongyu Wang
- Cardiovascular Institute and Division of Cardiology,
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
- Department of Biostatistics, Boston University School of
Public Health, Boston, MA, USA
| | - Jenna N. McNeill
- Division of Cardiology, Department of Medicine,
Massachusetts General Hospital, Boston, MA, USA
- Pulmonary and Critical Care, Division of Massachusetts
General Hospital, Boston, MA, USA
| | - Rajeev Malhotra
- Division of Cardiology, Department of Medicine,
Massachusetts General Hospital, Boston, MA, USA
| | - Matthew Nayor
- Sections of Cardiovascular Medicine and Preventive Medicine
and Epidemiology, Department of Medicine, Boston University School of Medicine,
Boston, MA, USA
| | - Gregory D. Lewis
- Division of Cardiology, Department of Medicine,
Massachusetts General Hospital, Boston, MA, USA
| | - Jennifer E. Ho
- Cardiovascular Institute and Division of Cardiology,
Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA
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Dziedziejko V, Safranow K, Kijko-Nowak M, Malinowski D, Domanski L, Pawlik A. Leptin receptor gene polymorphisms in kidney transplant patients with post-transplant diabetes mellitus treated with tacrolimus. Int Immunopharmacol 2023; 124:110989. [PMID: 37776770 DOI: 10.1016/j.intimp.2023.110989] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Revised: 08/17/2023] [Accepted: 09/22/2023] [Indexed: 10/02/2023]
Abstract
Post-transplant diabetes mellitus (PTDM) is a metabolic complication that often occurs after kidney transplantation. Factors that increase the risk of this complication are currently being researched, including polymorphisms in genes affecting carbohydrate-lipid metabolism. Leptin is a hormone that affects appetite and adipose tissue and plays an important role in regulating insulin secretion as well as glucose and lipid metabolism. The aim of this study was to examine the association between leptin receptor gene polymorphisms and the development of post-transplant diabetes mellitus in patients treated with tacrolimus. The study was carried out in a group of 201 patients who underwent kidney transplantation. The follow-up period was 12 months. PTDM was diagnosed in 35 patients. Analysing the LEPR gene rs1137101 polymorphism, we observed in patients with PTDM an increased frequency of GG genotype carriers (GG vs AA, OR 3.36; 95 % CI 0.99-11.46; p = 0.04). There were no statistically significant differences in the distribution of the LEPR rs1137100 and LEPR rs1805094 polymorphisms between patients with and without PTDM. Multivariate regression analysis confirmed that female sex, advanced age, increased BMI and a higher number of LEPR rs1137101 G alleles were independent risk factors for PTDM development. The risk of PTDM development was almost 3.5 times greater in LEPR rs1137101 G allele carriers than in AA homozygotes (GG + AG vs AA; OR 3.48; 95 %CI (1.09-11.18), p = 0.035). The results suggest that patients after kidney transplantation with the LEPR gene rs1137101 G allele may have an increased risk of post-transplant diabetes development.
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Affiliation(s)
- Violetta Dziedziejko
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Krzysztof Safranow
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Mirosława Kijko-Nowak
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Damian Malinowski
- Department of Experimental and Clinical Pharmacology, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Leszek Domanski
- Department of Nephrology, Transplantology and Internal Medicine, Pomeranian Medical University, 70-111 Szczecin, Poland.
| | - Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, 70-111 Szczecin, Poland.
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11
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Kim D, Memili A, Chen HH, Highland HM, Polikowsky HG, Anwar MY, Laing ST, Lee M, McCormick JB, Fisher-Hoch SP, Below JE, North KE, Gutierrez AD. Sex-specific associations between adipokine profiles and carotid-intima media thickness in the Cameron County Hispanic Cohort (CCHC). Cardiovasc Diabetol 2023; 22:231. [PMID: 37653519 PMCID: PMC10472619 DOI: 10.1186/s12933-023-01968-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/22/2023] [Accepted: 08/16/2023] [Indexed: 09/02/2023] Open
Abstract
BACKGROUND Adipokines are hormones secreted from adipose tissue and are associated with cardiometabolic diseases (CMD). Functional differences between adipokines (leptin, adiponectin, and resistin) are known, but inconsistently reported associations with CMD and lack of studies in Hispanic populations are research gaps. We investigated the relationship between subclinical atherosclerosis and multiple adipokine measures. METHODS Cross-sectional data from the Cameron County Hispanic Cohort (N = 624; mean age = 50; Female = 70.8%) were utilized to assess associations between adipokines [continuous measures of adiponectin, leptin, resistin, leptin-to-adiponectin ratio (LAR), and adiponectin-resistin index (ARI)] and early atherosclerosis [carotid-intima media thickness (cIMT)]. We adjusted for sex, age, body mass index (BMI), smoking status, cytokines, fasting blood glucose levels, blood pressure, lipid levels, and medication usage in the fully adjusted linear regression model. We conducted sexes-combined and sex-stratified analyses to account for sex-specificity and additionally tested whether stratification of participants by their metabolic status (metabolically elevated risk for CMD as defined by having two or more of the following conditions: hypertension, dyslipidemia, insulin resistance, and inflammation vs. not) influenced the relationship between adipokines and cIMT. RESULTS In the fully adjusted analyses, adiponectin, leptin, and LAR displayed significant interaction by sex (p < 0.1). Male-specific associations were between cIMT and LAR [β(SE) = 0.060 (0.016), p = 2.52 × 10-4], and female-specific associations were between cIMT and adiponectin [β(SE) = 0.010 (0.005), p = 0.043] and ARI [β(SE) = - 0.011 (0.005), p = 0.036]. When stratified by metabolic health status, the male-specific positive association between LAR and cIMT was more evident among the metabolically healthy group [β(SE) = 0.127 (0.015), p = 4.70 × 10-10] (p for interaction by metabolic health < 0.1). However, the female-specific associations between adiponectin and cIMT and ARI and cIMT were observed only among the metabolically elevated risk group [β(SE) = 0.014 (0.005), p = 0.012 for adiponectin; β(SE) = - 0.015 (0.006), p = 0.013 for ARI; p for interaction by metabolic health < 0.1]. CONCLUSION Associations between adipokines and cIMT were sex-specific, and metabolic health status influenced the relationships between adipokines and cIMT. These heterogeneities by sex and metabolic health affirm the complex relationships between adipokines and atherosclerosis.
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Affiliation(s)
- Daeeun Kim
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Aylin Memili
- Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, USA
| | - Hung-Hsin Chen
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Heather M Highland
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Hannah G Polikowsky
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Mohammad Yaser Anwar
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Susan T Laing
- Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX, USA
| | - Miryoung Lee
- Department of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston School of Public Health, Brownsville Regional Campus, Brownsville, TX, USA
| | - Joseph B McCormick
- Department of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston School of Public Health, Brownsville Regional Campus, Brownsville, TX, USA
| | - Susan P Fisher-Hoch
- Department of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas Health Science Center at Houston School of Public Health, Brownsville Regional Campus, Brownsville, TX, USA
| | - Jennifer E Below
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Kari E North
- Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Absalon D Gutierrez
- Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Texas Health Science Center at Houston McGovern Medical School, Houston, TX, USA.
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Quispe R, Sweeney T, Martin SS, Jones SR, Allison MA, Budoff MJ, Ndumele CE, Elshazly MB, Michos ED. Associations of Adipokine Levels with Levels of Remnant Cholesterol: the Multi-Ethnic Study of Atherosclerosis (MESA). MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.04.24.23289072. [PMID: 37162928 PMCID: PMC10168480 DOI: 10.1101/2023.04.24.23289072] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/11/2023]
Abstract
Background The metabolic syndrome phenotype of individuals with obesity is characterized by elevated levels of triglyceride (TG)-rich lipoproteins and remnant particles, which have been shown to be significantly atherogenic. Understanding the association between adipokines, endogenous hormones produced by adipose tissue, and remnant cholesterol (RC) would give insight into the link between obesity and atherosclerotic cardiovascular disease. Methods We studied 1,791 MESA participants of an ancillary study on body composition who had adipokine levels measured (leptin, adiponectin, resistin) at either visit 2 or 3. RC was calculated as non-high density lipoprotein cholesterol minus low-density lipoprotein cholesterol (LDL-C), measured at the same visit as the adipokines, as well as subsequent visits 4 through 6. Multivariable-adjusted linear mixed effects models were used to assess the cross-sectional and longitudinal associations between adipokines and levels of RC. Results Mean (SD) age was 64.5±9.6 years and for body mass index (BMI) was 29.9±5.0 kg/m2; 52.0% were women. In fully adjusted models that included BMI, LDL-C and lipid-lowering therapy, for each 1-unit increment in adiponectin, there was 14.4% (12.0, 16.8) lower RC. With each 1-unit increment in leptin and resistin, there was 4.5% (2.3, 6.6) and 5.1% (1.2, 9.2) higher RC, respectively. Lower adiponectin and higher leptin were also associated with longitudinal increases in RC levels over median follow-up of 5(4-8) years. Conclusions Lower adiponectin and higher leptin levels were independently associated with higher levels of RC at baseline and longitudinal RC increase, even after accounting for BMI and LDL-C. CLINICAL PERSPECTIVE What is new?: - Among individuals without history of cardiovascular disease, adiponectin is inversely associated with cross-sectional levels of remnant cholesterol, whereas leptin and resistin are directly associated.- Adiponectin had an inverse association with progression of remnant cholesterol levels over time.What are the clinical implications?: - Adiponectin levels were not associated with LDL-C levels but with levels of triglyceride-rich lipoproteins, particularly remnant cholesterol.-Incrementing adiponectin via lifestyle modification and/or pharmacological therapies (i.e. GLP-1 agonists) could be a mechanism to reduce remnant cholesterol levels and ultimately cardiovascular risk.
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Broni EK, Ogunmoroti O, Quispe R, Sweeney T, Varma B, Fashanu OE, Lutsey PL, Matthew Allison, Moyses Szklo, Ndumele CE, Michos ED. Adipokines and incident venous thromboembolism: The Multi-Ethnic Study of Atherosclerosis. J Thromb Haemost 2023; 21:303-310. [PMID: 36700499 PMCID: PMC10152466 DOI: 10.1016/j.jtha.2022.11.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2022] [Revised: 10/25/2022] [Accepted: 11/03/2022] [Indexed: 01/26/2023]
Abstract
BACKGROUND Obesity leads to adipocyte hypertrophy and adipokine dysregulation and is an independent risk factor for venous thromboembolism (VTE). However, the association between adipokines and VTE is not well established. OBJECTIVES To examine whether adipokines are associated with increased risk of incident VTE. METHODS We studied 1888 participants of the Multi-Ethnic Study of Atherosclerosis cohort who were initially free of VTE and had adipokine (adiponectin, leptin, and resistin) levels measured at either examination 2 or 3 (2002-2004 or 2004-2005, respectively). During follow-ups, VTE was ascertained through hospitalization records and death certificates by using ICD-9 and 10 codes. We used multivariable Cox proportional hazards regression to assess the association between 1 standard deviation (SD) log-transformed increments in adipokines and incident VTE. RESULTS The mean ± SD age was 64.7 ± 9.6 years, and 49.8% of participants were women. Medians (interquartile range) of adiponectin, leptin, and resistin were 17.3 (11.8-26.2) mcg/mL, 13.5 (5.6-28.2) ng/mL, and 15.0 (11.9-19.0) ng/mL, respectively. There were 78 incident cases of VTE after a median of 9.7 (5.0-12.4) years of follow-up. After adjusting for sociodemographics, smoking, and physical activity, the hazard ratios (95% CIs) per 1 SD increment of adiponectin, leptin, and resistin were 1.14 (0.90-1.44), 1.29 (1.00-1.66), and 1.38 (1.09-1.74), respectively. The association for resistin persisted after further adjustments for body mass index and computed tomography-derived total visceral adipose tissue area. CONCLUSION Higher resistin levels were independently associated with greater risk of incident VTE. Larger prospective cohort studies are warranted to confirm this association.
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Affiliation(s)
- Eric K Broni
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Oluseye Ogunmoroti
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Renato Quispe
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Ty Sweeney
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Bhavya Varma
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Oluwaseun E Fashanu
- Division of Cardiology, Rochester General Hospital, Rochester, New York, USA
| | - Pamela L Lutsey
- Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota, USA
| | - Matthew Allison
- Department of Family Medicine, University of California San Diego, La Jolla, California, USA
| | - Moyses Szklo
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
| | - Chiadi E Ndumele
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Erin D Michos
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
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Abe Y, Tonouchi R, Hara M, Okada T, Jego EH, Taniguchi T, Koshinaga T, Morioka I. Visceral Fat Area Measured by Abdominal Bioelectrical Impedance Analysis in School-Aged Japanese Children. J Clin Med 2022; 11:jcm11144148. [PMID: 35887911 PMCID: PMC9323507 DOI: 10.3390/jcm11144148] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2022] [Revised: 07/13/2022] [Accepted: 07/15/2022] [Indexed: 02/05/2023] Open
Abstract
Abdominal bioelectrical impedance analysis (aBIA) has been in use to measure visceral fat area (VFA) in adults. Accurately measuring visceral fat using aBIA in children is challenging. Forty-six school-aged Japanese children aged 6–17 years (25 boys and 21 girls) were included in this study. All were measured, and their VFA obtained using aBIA (VFA-aBIA) and abdominal computed tomography (CT) (VFA-CT) were compared. VFA-aBIA was corrected using the Passing–Bablok method (corrected VFA-aBIA). The relationships between corrected VFA-aBIA and obesity-related clinical factors were analyzed, including non-alcoholic fatty liver disease (NAFLD) and serum leptin and adiponectin levels. Boys had higher VFA-CT than girls (p = 0.042), although no significant differences were found in their waist circumference, waist-to-height ratio, and body mass index. The corrected VFA-aBIA using y = 9.600 + 0.3825x (boys) and y = 7.607 + 0.3661x (girls) correlated with VFA-CT in both boys and girls. The corrected VFA-aBIA in patients with NAFLD was higher than that in those without NAFLD. Serum leptin and adiponectin levels were positively and negatively correlated with corrected VFA-aBIA, respectively. In conclusion, corrected VFA-aBIA was clearly correlated with VFA-CT and was related to NAFLD and serum leptin and adiponectin levels in school-aged Japanese children.
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Affiliation(s)
- Yuriko Abe
- Division of Medical Education, Nihon University School of Medicine, Tokyo 173-8610, Japan;
- Medical Education Center, Nihon University School of Medicine, Tokyo 173-8610, Japan;
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo 173-8610, Japan; (R.T.); (M.H.); (T.O.)
| | - Ryousuke Tonouchi
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo 173-8610, Japan; (R.T.); (M.H.); (T.O.)
| | - Mitsuhiko Hara
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo 173-8610, Japan; (R.T.); (M.H.); (T.O.)
- Department of Health and Nutrition, Faculty of Human Ecology, Wayo Women’s University, Ichikawa 272-8533, Japan
| | - Tomoo Okada
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo 173-8610, Japan; (R.T.); (M.H.); (T.O.)
| | - Eric H. Jego
- Medical Education Center, Nihon University School of Medicine, Tokyo 173-8610, Japan;
| | - Tetsuya Taniguchi
- Department of Liberal Arts, Nihon University School of Medicine, Tokyo 173-8610, Japan;
| | - Tsugumichi Koshinaga
- Department of Pediatric Surgery, Nihon University School of Medicine, Tokyo 173-8610, Japan;
| | - Ichiro Morioka
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo 173-8610, Japan; (R.T.); (M.H.); (T.O.)
- Correspondence: ; Tel.: +81-3-3972-8111; Fax: +81-3-3958-5744
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15
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Liu L, Shi Z, Ji X, Zhang W, Luan J, Zahr T, Qiang L. Adipokines, adiposity, and atherosclerosis. Cell Mol Life Sci 2022; 79:272. [PMID: 35503385 PMCID: PMC11073100 DOI: 10.1007/s00018-022-04286-2] [Citation(s) in RCA: 78] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 03/11/2022] [Accepted: 04/03/2022] [Indexed: 12/12/2022]
Abstract
Characterized by a surplus of whole-body adiposity, obesity is strongly associated with the prognosis of atherosclerosis, a hallmark of coronary artery disease (CAD) and the major contributor to cardiovascular disease (CVD) mortality. Adipose tissue serves a primary role as a lipid-storage organ, secreting cytokines known as adipokines that affect whole-body metabolism, inflammation, and endocrine functions. Emerging evidence suggests that adipokines can play important roles in atherosclerosis development, progression, as well as regression. Here, we review the versatile functions of various adipokines in atherosclerosis and divide these respective functions into three major groups: protective, deteriorative, and undefined. The protective adipokines represented here are adiponectin, fibroblast growth factor 21 (FGF-21), C1q tumor necrosis factor-related protein 9 (CTRP9), and progranulin, while the deteriorative adipokines listed include leptin, chemerin, resistin, Interleukin- 6 (IL-6), and more, with additional adipokines that have unclear roles denoted as undefined adipokines. Comprehensively categorizing adipokines in the context of atherosclerosis can help elucidate the various pathways involved and potentially pave novel therapeutic approaches to treat CVDs.
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Affiliation(s)
- Longhua Liu
- School of Kinesiology, Shanghai University of Sport, Shanghai, People's Republic of China.
| | - Zunhan Shi
- School of Kinesiology, Shanghai University of Sport, Shanghai, People's Republic of China
| | - Xiaohui Ji
- School of Kinesiology, Shanghai University of Sport, Shanghai, People's Republic of China
| | - Wenqian Zhang
- School of Kinesiology, Shanghai University of Sport, Shanghai, People's Republic of China
| | - Jinwen Luan
- School of Kinesiology, Shanghai University of Sport, Shanghai, People's Republic of China
| | - Tarik Zahr
- Department of Pharmacology, Columbia University, New York, NY, USA
| | - Li Qiang
- Department of Pathology and Cellular Biology and Naomi Berrie Diabetes Center, Columbia University, New York, NY, USA.
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16
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Rodriguez CP, Ogunmoroti O, Quispe R, Osibogun O, Ndumele CE, Echouffo Tcheugui J, Minhas AS, Bertoni AG, Allison MA, Michos ED. The Association Between Multiparity and Adipokine Levels: The Multi-Ethnic Study of Atherosclerosis. J Womens Health (Larchmt) 2022; 31:741-749. [PMID: 34747649 PMCID: PMC9133972 DOI: 10.1089/jwh.2021.0091] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022] Open
Abstract
Background: Multiparity is a risk factor for cardiovascular disease (CVD). However, the mechanisms of this relationship are unknown. Adipokines may predispose multiparous women to certain cardiometabolic complications that can increase their risk of future CVD. Materials and Methods: We studied 973 female participants of the Multi-Ethnic Study of Atherosclerosis free of CVD, who had complete data on parity and adipokines measured at Examination 2 or 3 (randomly assigned). Parity was categorized as nulliparity, 1-2, 3-4, and ≥5 live births. Multivariable linear regression was used to evaluate the association of parity with leptin, resistin, and adiponectin levels. Results: The women had mean age of 65 ± 9 years. After adjustment for age, race/ethnicity, study site, education, menopause status, smoking, physical activity, use of hormone therapy, and waist circumference, a history of grand multiparity (≥5 live births) was associated with 11% higher resistin levels (95% confidence interval [CI] 0-23) and 3-4 live births was associated with 23% higher leptin levels (95% CI 7-42), compared with nulliparity. After adjustment for computed tomography-measured visceral fat, the association of 3-4 live births with leptin remained significant. There were no significant associations of parity with adipokines after further adjustment for additional CVD risk factors. Multigravidity (but not parity) was inversely associated with adiponectin levels. Conclusions: In a multiethnic cohort of women, greater parity was associated with resistin and leptin; however, this association was attenuated after accounting for CVD risk factors. Dysregulation of adipokines could contribute to the excess CVD risk associated with multiparity. Further studies are needed to determine whether adipokines independently mediate the relationship between multiparity and CVD. Clinical trials registration: The MESA cohort is registered at NCT00005487.
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Affiliation(s)
- Carla P. Rodriguez
- Division of Cardiology, The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Oluseye Ogunmoroti
- Division of Cardiology, The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Renato Quispe
- Division of Cardiology, The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Olatokunbo Osibogun
- Department of Epidemiology, Robert Stempel College of Public Health, Florida International University, Miami, Florida, USA
| | - Chiadi E. Ndumele
- Division of Cardiology, The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Justin Echouffo Tcheugui
- Division of Cardiology, The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Anum S. Minhas
- Division of Cardiology, The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
| | - Alain G. Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, North Carolina, USA
| | - Matthew A. Allison
- Department of Family Medicine, University of California San Diego, San Diego, California, USA
| | - Erin D. Michos
- Division of Cardiology, The Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
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Abstract
The development of pulmonary hypertension (PH) is common and has adverse prognostic implications in patients with heart failure due to left heart disease (LHD), and thus far, there are no known treatments specifically for PH-LHD, also known as group 2 PH. Diagnostic thresholds for PH-LHD, and clinical classification of PH-LHD phenotypes, continue to evolve and, therefore, present a challenge for basic and translational scientists actively investigating PH-LHD in the preclinical setting. Furthermore, the pathobiology of PH-LHD is not well understood, although pulmonary vascular remodeling is thought to result from (1) increased wall stress due to increased left atrial pressures; (2) hemodynamic congestion-induced decreased shear stress in the pulmonary vascular bed; (3) comorbidity-induced endothelial dysfunction with direct injury to the pulmonary microvasculature; and (4) superimposed pulmonary arterial hypertension risk factors. To ultimately be able to modify disease, either by prevention or treatment, a better understanding of the various drivers of PH-LHD, including endothelial dysfunction, abnormalities in vascular tone, platelet aggregation, inflammation, adipocytokines, and systemic complications (including splanchnic congestion and lymphatic dysfunction) must be further investigated. Here, we review the diagnostic criteria and various hemodynamic phenotypes of PH-LHD, the potential biological mechanisms underlying this disorder, and pressing questions yet to be answered about the pathobiology of PH-LHD.
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Affiliation(s)
- Jessica H Huston
- Division of Cardiology, Department of Internal Medicine, University of Pittsburgh Medical Center, Pittsburgh, PA (J.H.H.)
| | - Sanjiv J Shah
- Division of Cardiology, Department of Medicine, Feinberg Cardiovascular and Renal Research Institute, Northwestern University Feinberg School of Medicine, Chicago, IL (S.J.S.)
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18
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Varma B, Ogunmoroti O, Ndumele CE, Zhao D, Szklo M, Sweeney T, Allison MA, Budoff MJ, Subramanya V, Bertoni AG, Michos ED. Higher Leptin Levels Are Associated with Coronary Artery Calcium Progression: the Multi-Ethnic Study of Atherosclerosis (MESA). DIABETES EPIDEMIOLOGY AND MANAGEMENT 2022; 6:100047. [PMID: 35132401 PMCID: PMC8817736 DOI: 10.1016/j.deman.2021.100047] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Adipokines play a role in cardiometabolic pathways. Coronary artery calcium (CAC) progression prognosticates cardiovascular disease (CVD) risk. However, the association of adipokines with CAC progression is not well established. We examined the association of adipokines with CAC progression in a multi-ethnic cohort free of CVD at baseline. METHODS We included 1,904 randomly-selected adults enrolled in the Multi-Ethnic Study of Atherosclerosis who had both adipokine levels [leptin, resistin, adiponectin] and CAC by CT measured at either exam 2 (2002-2004) or exam 3 (2004-2005). CAC was previously measured at exam 1 (2000-2002) and a subset (n=566) had CAC measured at exam 5 (2010-2012). We used logistic regression to examine odds of CAC progression between exam 1 and 2/3 (defined as >0 Agatston units of change/year). We used linear mixed effect models to examine CAC progression from exam 2/3 to 5. RESULTS At exam 2/3, the mean age was 65(10) yrs; 50% women. In models adjusted for sociodemographic factors and BMI, the highest tertile of leptin, compared to lowest, was associated with an increased odds of CAC progression over the preceding 2.6yrs [OR 1.60 (95% CI: 1.10-2.33)]. In models further adjusted for visceral fat and CVD risk factors, the highest tertile of leptin was statistically significantly associated with a 4% (1-7%) greater CAC progression over an average of 7yrs. No associations were seen for resistin and adiponectin. CONCLUSIONS Higher leptin levels were independently, but modestly, associated with CAC progression. Atherosclerosis progression may be one mechanism through which leptin confers increased CVD risk.
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Affiliation(s)
- Bhavya Varma
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Oluseye Ogunmoroti
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Chiadi E. Ndumele
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Di Zhao
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Moyses Szklo
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
| | - Ty Sweeney
- Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD
| | - Matthew A. Allison
- Department of Family Medicine, University of California San Diego, San Diego, CA
| | | | - Vinita Subramanya
- Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Alain G. Bertoni
- Department of Epidemiology & Prevention, Wake Forest School of Medicine, Winston Salem, NC
| | - Erin D. Michos
- Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
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The Roles and Associated Mechanisms of Adipokines in Development of Metabolic Syndrome. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27020334. [PMID: 35056647 PMCID: PMC8781412 DOI: 10.3390/molecules27020334] [Citation(s) in RCA: 72] [Impact Index Per Article: 24.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/09/2021] [Revised: 12/30/2021] [Accepted: 01/03/2022] [Indexed: 12/12/2022]
Abstract
Metabolic syndrome is a cluster of metabolic indicators that increase the risk of diabetes and cardiovascular diseases. Visceral obesity and factors derived from altered adipose tissue, adipokines, play critical roles in the development of metabolic syndrome. Although the adipokines leptin and adiponectin improve insulin sensitivity, others contribute to the development of glucose intolerance, including visfatin, fetuin-A, resistin, and plasminogen activator inhibitor-1 (PAI-1). Leptin and adiponectin increase fatty acid oxidation, prevent foam cell formation, and improve lipid metabolism, while visfatin, fetuin-A, PAI-1, and resistin have pro-atherogenic properties. In this review, we briefly summarize the role of various adipokines in the development of metabolic syndrome, focusing on glucose homeostasis and lipid metabolism.
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20
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Varma B, Ogunmoroti O, Ndumele CE, Kazzi B, Rodriquez CP, Osibogun O, Allison MA, Bertoni AG, Michos ED. Associations between endogenous sex hormone levels and adipokine levels in the Multi-Ethnic Study of Atherosclerosis. Front Cardiovasc Med 2022; 9:1062460. [PMID: 36712262 PMCID: PMC9880051 DOI: 10.3389/fcvm.2022.1062460] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2022] [Accepted: 12/29/2022] [Indexed: 01/14/2023] Open
Abstract
Background Differences in sex hormone levels contribute to differences in cardiovascular disease (CVD) risk. Adipokines play a role in cardiometabolic pathways and have differing associations with CVD. Adipokine levels differ by sex; however, the association between sex hormone profiles and adipokines is not well established. We hypothesized that a more androgenic sex hormone profile would be associated with higher leptin and resistin and lower adiponectin levels among postmenopausal women, with the opposite associations in men. Methods We performed an analysis of 1,811 adults in the Multi-Ethnic Study of Atherosclerosis who had both sex hormones and adipokines measured an average of 2.6 years apart. Sex hormones [Testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG), and dehydroepiandrosterone (DHEA)] were measured at exam 1; free T was estimated. Serum adipokines (leptin, resistin, adiponectin) were measured at exams 2 or 3. We used multivariable linear regression to examine the cross-sectional associations between sex hormones and adipokines. Results The mean (SD) age was 63 (10) years, 48% were women; 59% non-White participants. For leptin, after adjusting for demographics only, higher free T and lower SHBG, were associated with higher leptin in women; this association was attenuated after further covariate adjustment. However in men, higher free T and lower SHBG were associated with greater leptin levels in fully adjusted models. For adiponectin, lower free T and higher SHBG were associated with greater adiponectin in both women and men after adjustment for CVD risk factors. For resistin, no significant association was found women, but an inverse association with total T and bioT was seen in men. Conclusion Overall, these results further suggest a more androgenic sex profile (higher free T and lower SHBG) is associated with a less favorable adipokine pattern. These findings may provide mechanistic insight into the interplay between sex hormones, adipokines, and CVD risk.
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Affiliation(s)
- Bhavya Varma
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Oluseye Ogunmoroti
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Chiadi E Ndumele
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Brigitte Kazzi
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Carla P Rodriquez
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, United States
| | - Olatokunbo Osibogun
- Department of Epidemiology, Robert Stempel College of Public Health and Social Work, Florida International University, Miami, FL, United States
| | - Matthew A Allison
- Department of Family Medicine, University of California, San Diego, San Diego, CA, United States
| | - Alain G Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston-Salem, NC, United States
| | - Erin D Michos
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins School of Medicine, Baltimore, MD, United States
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21
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Sweeney T, Ogunmoroti O, Ndumele CE, Zhao D, Varma B, Allison MA, Budoff MJ, Fashanu OE, Sharma A, Bertoni AG, Michos ED. Associations of adipokine levels with the prevalence and extent of valvular and thoracic aortic calcification: The Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2021; 338:15-22. [PMID: 34785427 PMCID: PMC8665862 DOI: 10.1016/j.atherosclerosis.2021.11.002] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/04/2021] [Revised: 10/16/2021] [Accepted: 11/02/2021] [Indexed: 12/20/2022]
Abstract
BACKGROUND AND AIMS Extra-coronary calcification (ECC) is a marker of atherosclerosis and independently associated with cardiovascular disease (CVD). Adipokines may mediate the effect of obesity on atherosclerosis. However, the relationship of adipokines with ECC is not well-established. We examined the associations of leptin, resistin and adiponectin with ECC in a diverse community-based cohort. METHODS We performed a cross-sectional analysis of 1897 adults without clinical CVD in the MESA cohort. Serum adipokine levels and non-contrast cardiac CT scans were obtained at Exam 2 or 3 (randomly assigned). ECC was quantified by Agatston score and included calcification of the mitral annulus (MAC), aortic valve (AVC), ascending thoracic aorta (ATAC) and descending thoracic aorta (DTAC). We used multivariable regression to evaluate the associations between leptin, resistin and adiponectin [per 1 SD ln(adipokine] with ECC prevalence (score >0) and extent [ln(score+1)]. RESULTS The mean age of participants was 65 ± 10 years; 49% women. After adjusting for demographic factors, adiponectin was inversely associated with AVC prevalence and extent; leptin positively associated with MAC prevalence and extent; and resistin positively associated with ATAC prevalence and extent and DTAC extent. After adjustment for BMI and other CVD risk factors, adiponectin remained inversely associated with AVC prevalence, and resistin remained associated with greater ATAC prevalence and extent. Leptin was not associated with measures of ECC after full adjustment. No adipokine was associated with MAC after full adjustment. CONCLUSIONS We identified significant associations between select adipokines and specific markers of ECC. Adipokines may play a role in the development of systemic atherosclerosis.
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Affiliation(s)
- Ty Sweeney
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Oluseye Ogunmoroti
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Chiadi E Ndumele
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Di Zhao
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Bhavya Varma
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Matthew A Allison
- Department of Family Medicine, University of California San Diego, San Diego, CA, USA
| | | | | | - Apurva Sharma
- Icahn School of Medicine, Mount Sinai Hospital, New York City, NY, USA
| | - Alain G Bertoni
- Department of Epidemiology and Prevention, Wake Forest School of Medicine, Winston Salem, NC, USA
| | - Erin D Michos
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
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22
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Zyśk B, Ostrowska L, Smarkusz-Zarzecka J. Salivary Adipokine and Cytokine Levels as Potential Markers for the Development of Obesity and Metabolic Disorders. Int J Mol Sci 2021; 22:ijms222111703. [PMID: 34769133 PMCID: PMC8584047 DOI: 10.3390/ijms222111703] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2021] [Revised: 10/23/2021] [Accepted: 10/24/2021] [Indexed: 12/16/2022] Open
Abstract
Currently, the number of people suffering from obesity is increasing worldwide. In addition, the disease is affecting younger individuals. Therefore, it is essential to search for new diagnostic methods and markers for early assessment of the risk of obesity, metabolic disorders, and other comorbidities. The discovery of the secretory function of adipose tissue and coexistence of low-grade chronic inflammation with obesity set a new direction in this disease diagnosis using the assessment of the concentration of inflammatory markers secreted by adipose tissue. The aim of this review was to determine, based on previous findings, whether saliva can be useful in the diagnosis of obesity and its early metabolic complications and whether it can be an alternative diagnostic material to serum.
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23
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Bermúdez V, Durán P, Rojas E, Díaz MP, Rivas J, Nava M, Chacín M, Cabrera de Bravo M, Carrasquero R, Ponce CC, Górriz JL, D´Marco L. The Sick Adipose Tissue: New Insights Into Defective Signaling and Crosstalk With the Myocardium. Front Endocrinol (Lausanne) 2021; 12:735070. [PMID: 34603210 PMCID: PMC8479191 DOI: 10.3389/fendo.2021.735070] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2021] [Accepted: 08/30/2021] [Indexed: 12/12/2022] Open
Abstract
Adipose tissue (AT) biology is linked to cardiovascular health since obesity is associated with cardiovascular disease (CVD) and positively correlated with excessive visceral fat accumulation. AT signaling to myocardial cells through soluble factors known as adipokines, cardiokines, branched-chain amino acids and small molecules like microRNAs, undoubtedly influence myocardial cells and AT function via the endocrine-paracrine mechanisms of action. Unfortunately, abnormal total and visceral adiposity can alter this harmonious signaling network, resulting in tissue hypoxia and monocyte/macrophage adipose infiltration occurring alongside expanded intra-abdominal and epicardial fat depots seen in the human obese phenotype. These processes promote an abnormal adipocyte proteomic reprogramming, whereby these cells become a source of abnormal signals, affecting vascular and myocardial tissues, leading to meta-inflammation, atrial fibrillation, coronary artery disease, heart hypertrophy, heart failure and myocardial infarction. This review first discusses the pathophysiology and consequences of adipose tissue expansion, particularly their association with meta-inflammation and microbiota dysbiosis. We also explore the precise mechanisms involved in metabolic reprogramming in AT that represent plausible causative factors for CVD. Finally, we clarify how lifestyle changes could promote improvement in myocardiocyte function in the context of changes in AT proteomics and a better gut microbiome profile to develop effective, non-pharmacologic approaches to CVD.
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Affiliation(s)
- Valmore Bermúdez
- Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla, Colombia
| | - Pablo Durán
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Edward Rojas
- Cardiovascular Division, University Hospital, University of Virginia School of Medicine, Charlottesville, VA, United States
| | - María P. Díaz
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - José Rivas
- Department of Medicine, Cardiology Division, University of Florida-College of Medicine, Jacksonville, FL, United States
| | - Manuel Nava
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Maricarmen Chacín
- Facultad de Ciencias de la Salud, Universidad Simón Bolívar, Barranquilla, Colombia
| | | | - Rubén Carrasquero
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - Clímaco Cano Ponce
- Endocrine and Metabolic Diseases Research Center, School of Medicine, University of Zulia, Maracaibo, Venezuela
| | - José Luis Górriz
- Servicio de Nefrología, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, Valencia, Spain
| | - Luis D´Marco
- Servicio de Nefrología, Hospital Clínico Universitario, INCLIVA, Universidad de Valencia, Valencia, Spain
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24
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Sweeney T, Quispe R, Das T, Juraschek SP, Martin SS, Michos ED. The Use of Blood Biomarkers in Precision Medicine for the Primary Prevention of Atherosclerotic Cardiovascular Disease: a Review. EXPERT REVIEW OF PRECISION MEDICINE AND DRUG DEVELOPMENT 2021; 6:247-258. [PMID: 34423130 DOI: 10.1080/23808993.2021.1930531] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023]
Abstract
Introduction A biomarker is a substance, structure, or process that indicates the presence of a disease, infection, or environmental exposure. Clinically useful biomarkers are measurable, improve diagnostic or prognostic performance, and ultimately aid clinicians in determining the initiation, duration, or magnitude of therapy. Areas Covered The purpose of this review is to explore the roles of various blood biomarkers of atherosclerotic cardiovascular disease (ASCVD) and how their use may improve the precision with which clinicians can identify, treat, and ultimately prevent ASCVD. Our review will include lipid biomarkers, markers of cardiac injury and wall stress, markers of inflammation, and a few others. Expert Opinion Several biomarkers have recently been highlighted as "risk-enhancing factors" in the 2019 American College of Cardiology/American Heart Association Guideline for the Primary Prevention of ASCVD, which can help guide shared decision-making. These included elevated low-density lipoprotein cholesterol, triglycerides, lipoprotein(a), apolipoprotein B, or high-sensitivity C-reactive protein. However, some other biomarkers mentioned in this review are not commonly used despite showing initial promise as prognostic of ASCVD risk, as it is not clear how treatment decisions should be changed after their measurement among asymptomatic individuals. Future studies should focus on whether biomarker-directed management strategies can improve clinical outcomes.
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Affiliation(s)
- Ty Sweeney
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Renato Quispe
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Thomas Das
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Stephen P Juraschek
- Department of Medicine, Beth Israel Deaconess Medical Center/Harvard Medical School, Boston, MA
| | - Seth S Martin
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Erin D Michos
- Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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25
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Patoulias D, Stavropoulos K, Imprialos K, Athyros V, Grassos H, Doumas M, Faselis C. Inflammatory Markers in Cardiovascular Disease; Lessons Learned and Future Perspectives. Curr Vasc Pharmacol 2021; 19:323-342. [PMID: 32188386 DOI: 10.2174/1570161118666200318104434] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2020] [Revised: 02/24/2020] [Accepted: 02/24/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Cardiovascular disease (CVD) still remains the leading cause of morbidity and mortality worldwide. It is now established that inflammation plays a crucial role in atherosclerosis and atherothrombosis, and thus, it is closely linked to cardiovascular disease. OBJECTIVE The aim of the present review is to summarize and critically appraise the most relevant evidence regarding the potential use of inflammatory markers in the field of CVD. METHODS We conducted a comprehensive research of the relevant literature, searching MEDLINE from its inception until November 2018, primarily for meta-analyses, randomized controlled trials and observational studies. RESULTS Established markers of inflammation, mainly C-reactive protein, have yielded significant results both for primary and secondary prevention of CVD. Newer markers, such as lipoprotein-associated phospholipase A2, lectin-like oxidized low-density lipoprotein receptor-1, cytokines, myeloperoxidase, cell adhesion molecules, matrix metalloproteinases, and the CD40/CD40 ligand system, have been largely evaluated in human studies, enrolling both individuals from the general population and patients with established CVD. Some markers have yielded conflicting results; however, others are now recognized not only as promising biomarkers of CVD, but also as potential therapeutic targets, establishing the role of anti-inflammatory and pleiotropic drugs in CVD. CONCLUSION There is significant evidence regarding the role of consolidated and novel inflammatory markers in the field of diagnosis and prognosis of CVD. However, multimarker model assessment, validation of cut-off values and cost-effectiveness analyses are required in order for those markers to be integrated into daily clinical practice.
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Affiliation(s)
- Dimitrios Patoulias
- Second Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | | | - Konstantinos Imprialos
- Second Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | - Vasilios Athyros
- Second Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | | | - Michael Doumas
- Second Propedeutic Department of Internal Medicine, Aristotle University, Thessaloniki, Greece
| | - Charles Faselis
- VA Medical Center, and George Washington University, Washington, DC 20422, United States
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26
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Empringham B, Jennings WJ, Rajan R, Fleming AJ, Portwine C, Johnston DL, Zelcer SM, Rassekh SR, Tran V, Burrow S, Thabane L, Samaan MC. Leptin is Associated with the Tri-Ponderal Mass Index in Children: A Cross-Sectional Study. ADOLESCENT HEALTH MEDICINE AND THERAPEUTICS 2021; 12:9-15. [PMID: 33727877 PMCID: PMC7955735 DOI: 10.2147/ahmt.s289973] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/10/2020] [Accepted: 02/05/2021] [Indexed: 11/23/2022]
Abstract
Background Obesity is characterized by the disproportionate expansion of the fat mass and is most commonly diagnosed using the Body Mass Index (BMI) z-score or percentile in children. However, these measures associate poorly with the fat mass. This is important, as adiposity is a more robust predictor of cardiometabolic risk than BMI-based measures, but there are limited clinical measures of adiposity in children. A new measure, the Tri-ponderal Mass Index (TMI, kg/m3) has recently demonstrated robust prediction of adiposity in children. The aim of this study is to explore the association of leptin, a validated biomarker of the fat mass, with TMI. Methods One hundred and eight children and adolescents were included in this cross-sectional study. Height and weight were used to calculate TMI. Plasma leptin was measured using ELISA. Multivariable regression analysis was applied to determine the predictors of TMI. Results The age range of participants included in this study was 8.00-16.90 years (female n=48, 44%). Leptin correlated with BMI percentile (r=0.64, p-value <0.0001) and TMI (r=0.71, p-value <0.0001). The multivariable regression analysis revealed that BMI percentile (Estimated Beta-coefficient 0.002, 95% CI 0.002-0.003, p-value <0.0001) and Leptin (Estimated Beta-coefficient 0.05, 95% CI 0.02-0.07, p-value 0.013) were associated with TMI. Conclusion Leptin is associated with TMI in healthy children. The TMI is a feasible clinical measure of adiposity that may be used to stratify children and adolescents for further assessments and interventions to manage and attempt to prevent cardiometabolic comorbidities.
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Affiliation(s)
- Brianna Empringham
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.,Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - William J Jennings
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.,Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Raeesha Rajan
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.,Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada.,Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
| | - Adam J Fleming
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.,Division of Pediatric Hematology/Oncology, McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Carol Portwine
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.,Division of Pediatric Hematology/Oncology, McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Donna L Johnston
- Division of Pediatric Hematology/Oncology, Children's Hospital of Eastern Ontario, Ottawa, Ontario, Canada
| | - Shayna M Zelcer
- Pediatric Hematology Oncology, Children's Hospital, London Health Sciences Center, London, Ontario, Canada
| | - Shahrad Rod Rassekh
- Division of Pediatric Hematology/Oncology/BMT, Department of Pediatrics, British Columbia's Children's Hospital, Vancouver, BC, Canada
| | - Victoria Tran
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.,Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada
| | - Sarah Burrow
- Division of Orthopedic Surgery, Department of Surgery, McMaster University Medical Centre, Hamilton, Ontario, Canada
| | - Lehana Thabane
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada.,Department of Anesthesia, McMaster University, Hamilton, Ontario, Canada.,Centre for Evaluation of Medicines, St. Joseph's Health Care, Hamilton, Ontario, Canada.,Biostatistics Unit, St Joseph's Healthcare-Hamilton, Hamilton, Ontario, Canada
| | - M Constantine Samaan
- Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.,Division of Pediatric Endocrinology, McMaster Children's Hospital, Hamilton, Ontario, Canada.,Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada
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27
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Perakakis N, Farr OM, Mantzoros CS. Leptin in Leanness and Obesity: JACC State-of-the-Art Review. J Am Coll Cardiol 2021; 77:745-760. [PMID: 33573745 DOI: 10.1016/j.jacc.2020.11.069] [Citation(s) in RCA: 99] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Accepted: 11/04/2020] [Indexed: 12/12/2022]
Abstract
Leptin has emerged over the past 2 decades as a key hormone secreted by adipose tissue that conveys information on energy stores. Leptin is considered an important regulator of both neuroendocrine function and energy homeostasis. Numerous studies (mainly preclinical and much less in humans) have investigated the mechanisms of leptin's actions both in the healthy state as well as in a wide range of metabolic diseases. In this review, the authors present leptin physiology and review the main findings from animal studies, observational and interventional studies, and clinical trials in humans that have investigated the role of leptin in metabolism and cardiometabolic diseases (energy deficiency, obesity, diabetes, cardiovascular diseases, nonalcoholic fatty liver disease). The authors discuss the similarities and discrepancies between animal and human biology and present clinical applications of leptin, directions for future research, and current approaches for the development of the next-generation leptin analogs.
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Affiliation(s)
- Nikolaos Perakakis
- Department of Medicine, Boston VA Healthcare System, Boston, Massachusetts, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Olivia M Farr
- Department of Medicine, Boston VA Healthcare System, Boston, Massachusetts, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
| | - Christos S Mantzoros
- Department of Medicine, Boston VA Healthcare System, Boston, Massachusetts, USA; Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
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28
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Kang KW, Ok M, Lee SK. Leptin as a Key between Obesity and Cardiovascular Disease. J Obes Metab Syndr 2020; 29:248-259. [PMID: 33342767 PMCID: PMC7789022 DOI: 10.7570/jomes20120] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2020] [Revised: 12/03/2020] [Accepted: 12/13/2020] [Indexed: 12/14/2022] Open
Abstract
Obesity increases the risk of cardiovascular disease through various influencing factors. Leptin, which is predominantly secreted by adipose tissue, regulates satiety homeostasis and energy balance, and influences cardiovascular functions directly and indirectly. Leptin appears to play a role in heart protection in leptin-deficient and leptin-receptor-deficient rodent model experiments. Hyperleptinemia or leptin resistance in human obesity influences the vascular endothelium, cardiovascular structure and functions, inflammation, and sympathetic activity, which may lead to cardiovascular disease. Leptin is involved in many processes, including signal transduction, vascular endothelial function, and cardiac structural remodeling. However, the dual (positive and negative) regulator effect of leptin and its receptor on cardiovascular disease has not been completely understood. The protective role of leptin signaling in cardiovascular disease could be a promising target for cardiovascular disease prevention in obese patients.
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Affiliation(s)
- Ki-Woon Kang
- Division of Cardiology, Department of Internal Medicine, Eulji University School of Medicine, Daejeon, Korea
| | - Minho Ok
- Department of Cardiovascular Pharmacology, Mokpo National University, Mokpo, Korea
| | - Seong-Kyu Lee
- Division of Endocrinology, Department of Internal Medicine, Daejeon, Korea.,Department of Biochemistry-Molecular Biology, Eulji University School of Medicine, Daejeon, Korea
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29
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Liew CH, Sim WH, Low EZ, Chan BCM. Leptin and cardiovascular health in high body mass index. Ir J Med Sci 2020; 190:441-442. [PMID: 32617853 DOI: 10.1007/s11845-020-02288-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2020] [Accepted: 06/18/2020] [Indexed: 10/23/2022]
Affiliation(s)
- Chee H Liew
- School of Medicine, National University of Ireland Galway, Galway, Ireland. .,National Institute for Prevention and Cardiovascular Health, Galway, Ireland. .,School of Medicine, Trinity College Dublin, Dublin, Ireland.
| | - Wee H Sim
- Department of Medicine, University Hospital Limerick, Limerick, Ireland
| | - Ernest Z Low
- Department of Geriatric Medicine, Letterkenny University Hospital, Letterkenny, Ireland
| | - Bernard C M Chan
- Department of General Surgery, Our Lady of Lourdes Hospital, Drogheda, Ireland
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30
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Paduszyńska A, Sakowicz A, Banach M, Maciejewski M, Dąbrowa M, Bielecka-Dąbrowa A. Cardioprotective properties of leptin in patients with excessive body mass. Ir J Med Sci 2020; 189:1259-1265. [PMID: 32198598 PMCID: PMC7554003 DOI: 10.1007/s11845-020-02211-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Accepted: 03/11/2020] [Indexed: 11/25/2022]
Abstract
Background Adipose tissue is producing adipokines that play different roles in the pathophysiology of cardiovascular disease. Aims The study aimed to assess the role of selected biomarkers in hypertensive patients with overweight and obesity compared with those with normal body-mass index (BMI). Methods A total of 62 patients with BMI < 25 kg/m2 (median age 54 (46–58) yrs., 57% males) and 51 with BMI ≥ 25 kg/m2 (median age 53 (48–59) yrs., 37% males) were enrolled. Biochemical parameters, leptin, adiponectin, and resistin; asymmetric dimethylarginine; interleukin 6; and N-terminal propeptide of type III procollagen, were assessed in plasma. The evaluation of hemodynamic parameters was performed using SphygmoCor 9.0 tonometer. Echocardiography was performed using AlokaAlpha 10 Premier device. Results Overweight and obese patients had significantly higher concentration of leptin (34 vs 18 ng/ml; p = 0.03), ADMA (0.43 vs 0.38 μmol/l, p = 0.04), and lower concentration of adiponectin (5.3 vs 7 μg/ml, p = 0.01). The only significant difference in tonometry analysis was higher aortic pulse pressure (mmHg) in patients with BMI ≥ 25 kg/m2 group (34 vs 30; p = 0.03). These patients had also significantly lower peak systolic velocity and early diastolic velocity in tissue Doppler imaging of the right ventricle free wall at the level of the tricuspid annulus compared with controls (p = 0.02 and p = 0.001, respectively). The level of leptin is correlated negatively with the left ventricular mass index (LVMI) (R Spearman = − 0.5; p = 0.002) and PWV (R = − 0.4; p = 0.01) and ADMA with total and LDL cholesterol (R = − 0.42; p = 0.008), and adiponectin is correlated positively with HDL cholesterol (R = 0.67; p = 0.0001). Conclusions Leptin concentrations were inversely proportional to LVMI and PWV in patients with BMI < 25 kg/m2. Trial registration Clinicaltrials.gov study ID: NCT04175080.
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Affiliation(s)
- Aleksandra Paduszyńska
- Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland
| | - Agata Sakowicz
- Department of Medical Biotechnology, Medical University of Lodz, Lodz, Poland
| | - Maciej Banach
- Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland
- Department of Cardiology and Congenital Diseases of Adults, Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Marek Maciejewski
- Department of Cardiology and Congenital Diseases of Adults, Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland
| | - Marek Dąbrowa
- Department of Biopharmacy, Chair of Biopharmacy, Medical University of Lodz, Lodz, Poland
| | - Agata Bielecka-Dąbrowa
- Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Lodz, Poland.
- Department of Cardiology and Congenital Diseases of Adults, Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
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Adipokines and Adipose Tissue-Related Metabolites, Nuts and Cardiovascular Disease. Metabolites 2020; 10:metabo10010032. [PMID: 31940832 PMCID: PMC7022531 DOI: 10.3390/metabo10010032] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2019] [Revised: 01/06/2020] [Accepted: 01/10/2020] [Indexed: 02/07/2023] Open
Abstract
Adipose tissue is a complex structure responsible for fat storage and releasing polypeptides (adipokines) and metabolites, with systemic actions including body weight balance, appetite regulation, glucose homeostasis, and blood pressure control. Signals sent from different tissues are generated and integrated in adipose tissue; thus, there is a close connection between this endocrine organ and different organs and systems such as the gut and the cardiovascular system. It is known that functional foods, especially different nuts, may be related to a net of molecular mechanisms contributing to cardiometabolic health. Despite being energy-dense foods, nut consumption has been associated with no weight gain, weight loss, and lower risk of becoming overweight or obese. Several studies have reported beneficial effects after nut consumption on glucose control, appetite suppression, metabolites related to adipose tissue and gut microbiota, and on adipokines due to their fatty acid profile, vegetable proteins, l-arginine, dietary fibers, vitamins, minerals, and phytosterols. The aim of this review is to briefly describe possible mechanisms implicated in weight homeostasis related to different nuts, as well as studies that have evaluated the effects of nut consumption on adipokines and metabolites related to adipose tissue and gut microbiota in animal models, healthy individuals, and primary and secondary cardiovascular prevention.
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Abstract
The adipocyte-derived adipokine leptin exerts pleiotropic effects, which are essential for the regulation of energy balance and cell metabolism, for controlling inflammatory and immune responses, and for the maintenance of homeostasis of the cardiovascular system. Leptin resistance in obese or type 2 diabetes mellitus (T2DM) patients is defined as a decrease in tissue response to leptin. In the cardiovascular system, leptin resistance exhibits the adverse effect on the heart's response to stress conditions and promoting cardiac remodeling due to impaired cardiac metabolism, increased fibrosis, vascular dysfunction, and enhanced inflammation. Leptin resistance or leptin signaling deficiency results in the risk increase of cardiac dysfunction and heart failure, which is a leading cause of obesity- and T2DM-related morbidity and mortality. Animal studies using leptin- and leptin receptor- (Lepr) deficient rodents have provided many useful insights into the underlying molecular and pathophysiological mechanisms of obese- and T2DM-associated metabolic and cardiovascular diseases. However, none of the animal models used so far can fully recapitulate the phenotypes of patients with obese or T2DM. Therefore, the role of leptin in the human cardiovascular system, and whether leptin affects cardiac function directly or acts through a leptin-regulated neurohumoral pathway, remain elusive. As the prevalence of obesity and diabetes is continuously increasing, strategies are needed to develop and apply human cell-based models to better understand the precise role of leptin directly in different cardiac cell types and to overcome the existing translational barriers. The purpose of this review is to discuss the mechanisms associated with leptin signaling deficiency or leptin resistance in the development of metabolic and cardiovascular diseases. We analyzed and comprehensively addressed substantial findings in pathophysiological mechanisms in commonly used leptin- or Lepr-deficient rodent models and highlighted the differences between rodents and humans. This may open up new strategies to develop directly and reliably applicable models, which resemble the human pathophysiology in order to advance health care management of obesity- and T2DM-related cardiovascular complications.
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Zhang T, Yang P, Li T, Gao J, Zhang Y. Leptin Expression in Human Epicardial Adipose Tissue Is Associated with Local Coronary Atherosclerosis. Med Sci Monit 2019; 25:9913-9922. [PMID: 31872802 PMCID: PMC6941777 DOI: 10.12659/msm.918390] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Background Leptin is an adipokine related to overweight and cardiovascular diseases. However, the leptin expression level in epicardial adipose tissue (EAT) of humans and its association with coronary atherosclerosis has never been investigated. Material/Methods Patients receiving cardiac surgery were divided into a coronary artery disease group (CAD group) and a non-CAD group (NCAD group). Blood samples from coronary vein, biopsies of subcutaneous adipose tissue (SAT), and EAT were acquired during the surgery. Serum leptin level and leptin level in EAT and SAT were tested with ELISA, quantitative PCR, and immunohistochemistry and were compared between the CAD group and NCAD group, as well as between stenosis and non-stenosis subgroups. Logistic regression analysis was performed to explore the risk factors for coronary artery stenosis. Results No statistically significant differences were found in demographic and clinical data between groups (all P>0.05). Serum leptin concentration and leptin expression in EAT and SAT of the CAD group were much higher in than in the NCAD group (all P<0.05). In subgroup analysis, there was no difference in serum leptin and expression in SAT of stenosis and non-stenosis patients (All P>0.05). The leptin expression level in EAT of stenosis patients was significantly higher than in non-stenosis patients (P=0.0431). By multivariate logistic regression analysis, we demonstrated that leptin expression level in EAT was an independent risk factor for coronary artery stenosis [OR=1.09, 95%CI (1.01±1.18), P=0.031]. Conclusions Leptin expression in EAT and SAT were both increased for CAD patients. Leptin expression in EAT was an independent risk factor for coronary atherosclerosis in the adjacent artery, while leptin in SAT was not associated.
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Affiliation(s)
- Tuowei Zhang
- Department of Cardiovascular Diseases, Xi'an Hospital of Traditional Chinese Medicine, Xi'an, Shangxi, China (mainland)
| | - Pengkang Yang
- Department of Cardiovascular Diseases, Xi'an No.1 Hospital, Xi'an, Shangxi, China (mainland)
| | - Tonghua Li
- Department of Cardiovascular Diseases, Xi'an No.1 Hospital, Xi'an, Shangxi, China (mainland)
| | - Jianping Gao
- Department of Cardiovascular Diseases, North of Weihe River Central Hospital, Xi'an, Shangxi, China (mainland)
| | - Yuyang Zhang
- Department of Cardiovascular Diseases, Xi'an No.1 Hospital, Xi'an, Shangxi, China (mainland)
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Che C, Dudick K, Shoemaker R. Cardiac hypertrophy with obesity is augmented after pregnancy in C57BL/6 mice. Biol Sex Differ 2019; 10:59. [PMID: 31842996 PMCID: PMC6916003 DOI: 10.1186/s13293-019-0269-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2019] [Accepted: 10/30/2019] [Indexed: 12/25/2022] Open
Abstract
BACKGROUND Over a third of reproductive-age women in the USA are obese, and the prevalence of cardiovascular disease (CVD) is rising in premenopausal women. Cardiac hypertrophy is an independent predictor of CVD. In contrast to pregnancy, where transiently increased left ventricular (LV) mass is not associated with cardiac damage, obesity-mediated cardiac hypertrophy is pathological. There is a paucity of data describing the effect of obesity during pregnancy on maternal cardiovascular health. The purpose of this study was to determine the long-term effect of obesity during pregnancy on cardiac function and structure in mice. METHODS Female C57BL/6 J mice were fed a high-fat (HF) or a low-fat (LF) diet for 20 weeks. After 4 weeks, LF- and HF-fed female mice were either crossed with males to become pregnant or remained non-pregnant controls. Following delivery, pups were euthanized, and females maintained on respective diets. After 20 weeks of diet feeding, cardiac function was quantified by echocardiography, and plasma leptin and adiponectin concentrations quantified in LF- and HF-fed postpartum and nulliparous females. mRNA abundance of genes regulating cardiac hypertrophy and remodeling was quantified from left ventricles using the NanoString nCounter Analysis System. Cardiac fibrosis was assessed from picrosirius red staining of left ventricles. RESULTS HF-fed postpartum mice had markedly greater weight gain and fat mass expansion with obesity, associated with significantly increased LV mass, cardiac output, and stroke volume compared with HF-fed nulliparous mice. Plasma leptin, but not adiponectin, concentrations were correlated with LV mass in HF-fed females. HF feeding increased LV posterior wall thickness; however, LV chamber diameter was only increased in HF-fed postpartum females. Despite the marked increase in LV mass in HF-fed postpartum mice, mRNA abundance of genes regulating fibrosis and interstitial collagen content was similar between HF-fed nulliparous and postpartum mice. In contrast, only HF-fed postpartum mice exhibited altered expression of genes regulating the extracellular matrix. CONCLUSIONS These results suggest that the combined effects of pregnancy and obesity augment cardiac hypertrophy and promote remodeling. The rising prevalence of CVD in premenopausal women may be attributed to an increased prevalence of women entering pregnancy with an overweight or obese BMI.
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Affiliation(s)
- Chen Che
- University of Kentucky, Department of Dietetics and Human Nutrition, 203 Funkhouser Bldg, Lexington, KY, 40506-0054, USA
| | - Kayla Dudick
- University of Kentucky, Department of Dietetics and Human Nutrition, 203 Funkhouser Bldg, Lexington, KY, 40506-0054, USA
| | - Robin Shoemaker
- University of Kentucky, Department of Dietetics and Human Nutrition, 203 Funkhouser Bldg, Lexington, KY, 40506-0054, USA.
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Sawaguchi T, Nakajima T, Haruyama A, Hasegawa T, Shibasaki I, Nakajima T, Kaneda H, Arikawa T, Obi S, Sakuma M, Ogawa H, Takei Y, Toyoda S, Nakamura F, Abe S, Fukuda H, Inoue T. Association of serum leptin and adiponectin concentrations with echocardiographic parameters and pathophysiological states in patients with cardiovascular disease receiving cardiovascular surgery. PLoS One 2019; 14:e0225008. [PMID: 31703113 PMCID: PMC6839852 DOI: 10.1371/journal.pone.0225008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2019] [Accepted: 10/25/2019] [Indexed: 11/18/2022] Open
Abstract
Leptin and adiponectin are important regulators of energy metabolism and body composition. Leptin exerts cardiodepressive effects, whereas adiponectin has cardioprotective effects, but several conflicting findings have been reported. The aim of the present study was to assess the relationship between serum leptin and adiponectin levels and echocardiographic parameters and pathophysiological states in patients with cardiovascular disease (CVD) receiving cardiovascular surgery. A total of 128 patients (79 males, average age 69.6 years) that had surgery for CVD including coronary artery bypass graft (CABG) and valve replacement were recruited in this study. Preoperative serum adiponectin and leptin concentrations were measured by enzyme-linked immunosorbent assay and compared with preoperative echocardiographic findings. Body fat volume and skeletal muscle volume index (SMI) were estimated using bioelectrical impedance analysis. We also measured grip strength and gait speed. Sarcopenia was diagnosed based on the recommendations of the Asian Working Group on Sarcopenia. Positive correlations were found between adiponectin and brain natriuretic peptide (BNP), age, left atrial diameter (LAD), E/e’ (early-diastolic left ventricular inflow velocity / early-diastolic mitral annular velocity), and left atrial volume index (LAVI). Negative correlations were observed between adiponectin and body mass index (BMI), estimated glomerular filtration rate (eGFR), triglyceride, hemoglobin, and albumin. Serum leptin was positively correlated with BMI, total cholesterol, triglyceride, albumin, body fat volume, and LV ejection fraction (LVEF), whereas it was negatively correlated with BNP and echocardiographic parameters (LAD, LV mass index (LVMI), and LAVI). Multiple regression analysis showed associations between log (leptin) and log (adiponectin) and echocardiographic parameters after adjusting for age, sex, and BMI. Serum adiponectin was negatively correlated with leptin, but positively correlated with tumor necrosis factor α (TNFα), an inflammatory cytokine. In males, serum leptin level had a positive correlation with skeletal muscle volume and SMI. However, adiponectin had a negative correlation with anterior mid-thigh muscle thickness, skeletal muscle volume and SMI. And, it was an independent predictive factor in males for sarcopenia even after adjusted by age. These results suggest that leptin and adiponectin may play a role in cardiac remodeling in CVD patients receiving cardiovascular surgery. And, adiponectin appears to be a marker of impaired metabolic signaling that is linked to heart failure progression including inflammation, poor nutrition, and muscle wasting in CVD patients receiving cardiovascular surgery.
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Affiliation(s)
- Tatsuya Sawaguchi
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Toshiaki Nakajima
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
- * E-mail:
| | - Akiko Haruyama
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Takaaki Hasegawa
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Ikuko Shibasaki
- Department of Cardiovascular Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Takafumi Nakajima
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Hiroyuki Kaneda
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Takuo Arikawa
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Syotaro Obi
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Masashi Sakuma
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Hironaga Ogawa
- Department of Cardiovascular Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Yuusuke Takei
- Department of Cardiovascular Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Shigeru Toyoda
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Fumitaka Nakamura
- Third Department of Internal Medicine, Teikyo University, Chiba Medical Center, Japan
| | - Shichiro Abe
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
| | - Hirotsugu Fukuda
- Department of Cardiovascular Surgery, Dokkyo Medical University, Tochigi, Japan
| | - Teruo Inoue
- Department of Cardiovascular Medicine, Dokkyo Medical University, Tochigi, Japan
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Landecho MF, Tuero C, Valentí V, Bilbao I, de la Higuera M, Frühbeck G. Relevance of Leptin and Other Adipokines in Obesity-Associated Cardiovascular Risk. Nutrients 2019; 11:nu11112664. [PMID: 31694146 PMCID: PMC6893824 DOI: 10.3390/nu11112664] [Citation(s) in RCA: 184] [Impact Index Per Article: 30.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2019] [Revised: 10/02/2019] [Accepted: 10/17/2019] [Indexed: 02/07/2023] Open
Abstract
Obesity, which is a worldwide epidemic, confers increased risk for multiple serious conditions including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular diseases. Adipose tissue is considered one of the largest endocrine organs in the body as well as an active tissue for cellular reactions and metabolic homeostasis rather than an inert tissue only for energy storage. The functional pleiotropism of adipose tissue relies on its ability to synthesize and release a large number of hormones, cytokines, extracellular matrix proteins, and growth and vasoactive factors, which are collectively called adipokines known to influence a variety of physiological and pathophysiological processes. In the obese state, excessive visceral fat accumulation causes adipose tissue dysfunctionality that strongly contributes to the onset of obesity-related comorbidities. The mechanisms underlying adipose tissue dysfunction include adipocyte hypertrophy and hyperplasia, increased inflammation, impaired extracellular matrix remodeling, and fibrosis together with an altered secretion of adipokines. This review describes the relevance of specific adipokines in the obesity-associated cardiovascular disease.
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Affiliation(s)
- Manuel F. Landecho
- Department of Internal Medicine, General Health Check-up Unit, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008 Pamplona, Navarra, Spain; (M.F.L.); (I.B.)
| | - Carlota Tuero
- Department of Surgery, Bariatric and Metabolic Surgery Unit, Clínica Universidad de Navarra, 31008 Pamplona, Navarra, Spain; (C.T.); (V.V.)
| | - Víctor Valentí
- Department of Surgery, Bariatric and Metabolic Surgery Unit, Clínica Universidad de Navarra, 31008 Pamplona, Navarra, Spain; (C.T.); (V.V.)
- Instituto de Salud Carlos III, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), 31008 Pamplona, Navarra, Spain
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Navarra, Spain
| | - Idoia Bilbao
- Department of Internal Medicine, General Health Check-up Unit, Clínica Universidad de Navarra, Avenida Pío XII, 36, 31008 Pamplona, Navarra, Spain; (M.F.L.); (I.B.)
| | - Magdalena de la Higuera
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, 28027 Madrid, Spain;
| | - Gema Frühbeck
- Obesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), 31008 Pamplona, Navarra, Spain
- Metabolic Research Laboratory, Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, Spain
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Pamplona, Spain
- Correspondence: ; Tel.: +0034-948-255-400
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Patoulias D, Imprialos K, Stavropoulos K, Doumas M. Serum leptin in non-alcoholic fatty liver disease: Ambiguous clinical implications concerning cardiovascular disease. Clin Mol Hepatol 2019; 25:331-332. [PMID: 31142103 PMCID: PMC6759434 DOI: 10.3350/cmh.2019.0034] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/22/2019] [Accepted: 04/08/2019] [Indexed: 11/05/2022] Open
Affiliation(s)
- Dimitrios Patoulias
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Konstantinos Imprialos
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Konstantinos Stavropoulos
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Michael Doumas
- Second Propedeutic Department of Internal Medicine, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece.,Veterans Affairs Medical Center, The George Washington University, Washington, D.C., WA, USA
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Belhayara MI, Mellouk Z, Hamdaoui MS, Bachaoui M, Kheroua O, Malaisse WJ. Relationship between the insulin resistance and circulating predictive biochemical markers in metabolic syndrome among young adults in western Algeria. Diabetes Metab Syndr 2019; 13:504-509. [PMID: 30641755 DOI: 10.1016/j.dsx.2018.11.019] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 11/02/2018] [Indexed: 01/31/2023]
Abstract
AIM The metabolic syndrome (MetS) becomes increasingly obvious from an early age. The current study aimed at exploring the relationship between insulin resistance and the main biomarkers of MetS in young adult algerian patients. METHODS Glucose, HbA1C, total cholesterol (TC), hjgh bensity lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), insulinemia and C-peptide, adipokins (leptin, adiponectin), inflammatory cytokines (IL-6 and TNF-a), us-CRP and GLP-1 were measured by suitable methods. Homeostasis model assessment (HOMA) was used to detect the degree of insulin resistance. RESULTS The MetS patients displayed higher glucose, insulin, HbA1c values and impaired lipid profile as judged by increasing TC, TG, LDL-C levels and lower HDL-C. Furthermore, adipokines, HDL-C and CRP contents were significantly higher whilst TG and LDL-C were much lower in MetS female group as compared to male patients suggesting most pronounced metabolic perturbation in the latter group. The probability of a significant correlation between HOMA and studied variables was often higher in female than male subjects. Such was the case for total cholesterol, HDL-cholesterol, triglycerides, adiponectin, interleukin-6, TNF-α and hs-CRP. CONCLUSION The high rate of metabolic syndrome among young obese adults is alarming, this requiring extensive investigations in prone subjects.
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Affiliation(s)
| | - Zoheir Mellouk
- Biology Department, Faculty of Natural and Life Sciences, University of Oran1, Algeria.
| | | | - Malika Bachaoui
- Department of Internal Medicine, University Hospital Institution of Oran, Algeria
| | - Omar Kheroua
- Biology Department, Faculty of Natural and Life Sciences, University of Oran1, Algeria
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Everson-Rose SA, Clark CJ, Wang Q, Guo H, Mancuso P, Kravitz HM, Bromberger JT. Depressive symptoms and adipokines in women: Study of women's health across the nation. Psychoneuroendocrinology 2018; 97:20-27. [PMID: 30005278 PMCID: PMC6300165 DOI: 10.1016/j.psyneuen.2018.07.011] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/19/2018] [Revised: 06/27/2018] [Accepted: 07/04/2018] [Indexed: 01/10/2023]
Abstract
Small clinical studies suggest depression is associated with alterations in adiponectin and leptin, adipocyte-derived secretory proteins involved in metabolic regulation; however, longitudinal data on these association are lacking. This study examined cross-sectional and longitudinal associations of depressive symptoms and major depressive disorder (MDD) with adiponectin and leptin in healthy middle-aged women (mean (SD) age, 45.6 (2.5) years). Cross-sectional analyses included 575 women with baseline adipokine data; longitudinal analyses included 262 women with 2-4 adipokine measurements over 5 years. The 20-item Center for Epidemiologic Studies Depression scale (CES-D) was used to assess depressive symptoms; history of MDD was determined by the Structured Clinical Interview for DSM-IV. Adipokines were assayed from stored serum specimens; values were log-transformed for analyses. Linear and repeated measure random effects regression models evaluated associations of baseline CES-D scores with baseline adipokine concentrations and changes over time, respectively. Secondary analyses evaluated the relation of MDD history with adipokine concentrations. Mean (SD) baseline concentrations of adiponectin and leptin were 9.90 (4.92) μg/mL and 27.02 (20.06) ng/mL; both increased over time (p < .0001). CES-D scores were associated with lower adiponectin at baseline (per 1-SD: estimate=-0.04, SE=.02, p=.03) and over time (per 1-SD: estimate=-0.055, SE = .024, p=.02). Associations were unchanged in risk factor-adjusted models. Women with elevated CES-D scores (≥16) had 6.9% (95% CI: -1.1%, 14.3%; p = .089) lower median adiponectin at baseline and 11.5% (95% CI: 1.5%, 20.4%, p = .025) lower median adiponectin over time in adjusted models, compared to women with CES-D<16. Rate of change in adipokines did not vary by baseline depressive symptoms or MDD history. Depressive symptoms and MDD history were unrelated to leptin. In women at midlife, depressive symptoms are associated with lower adiponectin, a critical anti-inflammatory biomarker involved in metabolic and cardiovascular conditions.
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Affiliation(s)
- Susan A. Everson-Rose
- Department of Medicine and Program in Health Disparities Research, University of Minnesota Medical School, Minneapolis, MN
| | - Cari J. Clark
- Hubert Department of Global Health, Rollins School of Public Health, Emory University, Atlanta, GA
| | - Qi Wang
- Biostatistical Design & Analysis Center, Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN
| | - Hongfei Guo
- Division of Biostatistics, School of Public Health, and Clinical and Translational Science Institute, University of Minnesota, Minneapolis, MN
| | - Peter Mancuso
- Department of Nutritional Sciences, University of Michigan School of Public Health, Ann Arbor, MI
| | - Howard M. Kravitz
- Department of Psychiatry and Department of Preventive Medicine, Rush Medical College, Rush University Medical Center, Chicago, IL
| | - Joyce T. Bromberger
- Departments of Epidemiology and Psychiatry, University of Pittsburgh, Pittsburgh, PA
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Liberale L, Carbone F, Bertolotto M, Bonaventura A, Vecchié A, Mach F, Burger F, Pende A, Spinella G, Pane B, Palombo D, Dallegri F, Montecucco F. Serum adiponectin levels predict acute coronary syndrome (ACS) in patients with severe carotid stenosis. Vascul Pharmacol 2018; 102:37-43. [PMID: 29305337 DOI: 10.1016/j.vph.2017.12.066] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2017] [Revised: 12/12/2017] [Accepted: 12/30/2017] [Indexed: 02/06/2023]
Abstract
As endocrine organ, adipose tissue may modulate inflammatory response by releasing a wide range of mediators, known as adipocytokines. Due to the complex balance between pro- and anti-inflammatory activity their pathophysiological and prognostic role in cardiovascular (CV) diseases still remains debated. Here, we consider the potential associations of circulating adipocytokines adiponectin, leptin and their ratio (LAR), with metabolic and inflammatory profiles in 217 patients with severe carotid stenosis. A prospective analysis investigating their predictive role toward acute coronary syndromes (ACS) was also drawn over a 12-month follow-up period. Serum leptin was positively associated with fasting insulinemia and HOMA-IR, but not with lipid profile and inflammation. Conversely, adiponectin was negatively associated with glucose, insulin, HOMA-IR, triglycerides and both systemic and intraplaque inflammatory markers whereas a positive association with high-density lipoprotein cholesterol (HDL-c) was observed. Accordingly, a significant association with metabolic profile was reported for LAR. According to the cut-off point identified by ROC curve, adiponectin values≤2.56μg/mL were correlated with a higher risk of ACS occurrence at 12months' follow-up (p-value for Log Rank test=0.0003). At Cox regression analysis the predictive ability of low serum adiponectin was confirmed also after adjustment for age, male gender and diabetes. In conclusion, adiponectin may be considered a biomarker of metabolic compensation, inversely associated with chronic low-grade inflammation. Circulating adiponectin is also associated with lower risk of adverse CV events in patients with severe carotid stenosis.
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Affiliation(s)
- Luca Liberale
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Center for Molecular Cardiology, University of Zürich, Wagistrasse 12, 8952 Schlieren, Switzerland.
| | - Federico Carbone
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Maria Bertolotto
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Aldo Bonaventura
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - Alessandra Vecchié
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy
| | - François Mach
- Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland
| | - Fabienne Burger
- Division of Cardiology, Foundation for Medical Researches, Department of Medical Specialties, University of Geneva, 64 Avenue de la Roseraie, 1211 Geneva, Switzerland
| | - Aldo Pende
- Clinic of Emergency Medicine, Department of Emergency Medicine, University of Genoa, 16132 Genoa, Italy; Ospedale Policlinico San Martino, 10 Largo Benzi, 16132 Genoa, Italy
| | - Giovanni Spinella
- Vascular and Endovascular Surgery Unit, Department of Surgery, University of Genoa, 16132 Genoa, Italy; Ospedale Policlinico San Martino, 10 Largo Benzi, 16132 Genoa, Italy
| | - Bianca Pane
- Vascular and Endovascular Surgery Unit, Department of Surgery, University of Genoa, 16132 Genoa, Italy; Ospedale Policlinico San Martino, 10 Largo Benzi, 16132 Genoa, Italy
| | - Domenico Palombo
- Vascular and Endovascular Surgery Unit, Department of Surgery, University of Genoa, 16132 Genoa, Italy; Ospedale Policlinico San Martino, 10 Largo Benzi, 16132 Genoa, Italy
| | - Franco Dallegri
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Ospedale Policlinico San Martino, 10 Largo Benzi, 16132 Genoa, Italy
| | - Fabrizio Montecucco
- First Clinic of Internal Medicine, Department of Internal Medicine, University of Genoa, 6 viale Benedetto XV, 16132 Genoa, Italy; Ospedale Policlinico San Martino, 10 Largo Benzi, 16132 Genoa, Italy; Centre of Excellence for Biomedical Research (CEBR), University of Genoa, 9 viale Benedetto XV, 16132 Genoa, Italy
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Ho JE, McCabe EL, Wang TJ, Larson MG, Levy D, Tsao C, Aragam J, Mitchell GF, Benjamin EJ, Vasan RS, Cheng S. Cardiometabolic Traits and Systolic Mechanics in the Community. Circ Heart Fail 2017; 10:CIRCHEARTFAILURE.116.003536. [PMID: 28495953 DOI: 10.1161/circheartfailure.116.003536] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/29/2016] [Accepted: 03/24/2017] [Indexed: 12/16/2022]
Abstract
BACKGROUND Obesity and cardiometabolic dysfunction are associated with increased risk of heart failure and other cardiovascular diseases. We sought to examine the association of cardiometabolic traits with left ventricular (LV) cardiac mechanics. We hypothesized that specific obesity-related phenotypes are associated with distinct aspects of LV strain. METHODS AND RESULTS We evaluated the associations of obesity-related phenotypes, including central adiposity, diabetes mellitus, insulin resistance, and circulating adipokine concentrations with echocardiographic measures of LV mechanical function among participants of the Framingham Heart Study Offspring and Third Generation cohorts. Among 6231 participants, the mean age was 51±16 years, and 54% were women. Greater body mass index was associated with worse LV longitudinal strain, radial strain (apical view), and longitudinal synchrony (multivariable-adjusted P<0.0001). After accounting for body mass index, we found that central adiposity, as measured by waist circumference, was associated with worse global longitudinal strain and synchrony (P≤0.006). Measures of insulin resistance, dyslipidemia, and diabetes mellitus also were associated with distinct aspects of LV mechanical function. Circulating leptin concentrations were associated with global longitudinal and radial strain (apical view, P<0.0001), whereas no such association was found with leptin receptor, adiponectin, or C-reactive protein. CONCLUSIONS Our findings highlight the association of central obesity and related cardiometabolic phenotypes above and beyond body mass index with subclinical measures of LV mechanical function. Interestingly, obesity-related traits were associated with distinct aspects of LV mechanics, underscoring potential differential effects along specific LV planes of deformation. These findings may shed light onto obesity-related cardiac remodeling and heart failure.
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Affiliation(s)
- Jennifer E Ho
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA.
| | - Elizabeth L McCabe
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Thomas J Wang
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Martin G Larson
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Daniel Levy
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Connie Tsao
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Jayashri Aragam
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Gary F Mitchell
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Emelia J Benjamin
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Ramachandran S Vasan
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
| | - Susan Cheng
- From the Cardiovascular Research Center and Cardiology Division, Department of Medicine, Massachusetts General Hospital, Boston (J.E.H.); National Heart, Lung, and Blood Institute's and Boston University's Framingham Heart Study, Framingham, MA (J.E.H., E.L.M., M.G.L., D.L., C.T., E.J.B., R.S.V., S.C.); Cardiology Division, Department of Medicine, Vanderbilt University, Nashville, TN (T.J.W.); Department of Biostatistics (M.G.L.) and Department of Epidemiology (E.J.B., R.S.V.), Boston University School of Public Health, MA; Cardiovascular Division, Beth Israel Deaconess Medical Center, Boston, MA (C.T.); Division of Cardiology, Department of Medicine, Brigham and Women's Hospital, Boston, MA (J.A., S.C.); Division of Cardiology, Department of Medicine, Veterans Affairs Boston Healthcare System, MA (J.A.); Cardiovascular Engineering, Inc, Norwood, MA (G.F.M.); and Cardiovascular Medicine Section (E.J.B.), Section of Preventive Medicine and Epidemiology (E.J.B., R.S.V.), and Section of Cardiology (E.J.B., R.S.V.), Department of Medicine, Boston University School of Medicine, MA
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Ruscica M, Baragetti A, Catapano AL, Norata GD. Translating the biology of adipokines in atherosclerosis and cardiovascular diseases: Gaps and open questions. Nutr Metab Cardiovasc Dis 2017; 27:379-395. [PMID: 28237179 DOI: 10.1016/j.numecd.2016.12.005] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2016] [Revised: 12/14/2016] [Accepted: 12/16/2016] [Indexed: 01/10/2023]
Abstract
AIM Critically discuss the available data, to identify the current gaps and to provide key concepts that will help clinicians in translating the biology of adipokines in the context of atherosclerosis and cardio-metabolic diseases. DATA SYNTHESIS Adipose tissue is nowadays recognized as an active endocrine organ, a function related to the ability to secrete adipokines (such as leptin and adiponectin) and pro-inflammatory cytokines (tumor necrosis factor alpha and resistin). Studies in vitro and in animal models have observed that obesity status presents a chronic low-grade inflammation as the consequence of the immune cells infiltrating the adipose tissue as well as adipocytes. This inflammatory signature is often related to the presence of cardiovascular diseases, including atherosclerosis and thrombosis. These links are less clear in humans, where the role of adipokines as prognostic marker and/or player in cardiovascular diseases is not as clear as that observed in experimental models. Moreover, plasma adipokine levels might reflect a condition of adipokine-resistance in which adipokine redundancy occurs. The investigation of the cardio-metabolic phenotype of carriers of single nucleotide polymorphisms affecting the levels or function of a specific adipokine might help determine their relevance in humans. Thus, the aim of the present review is to critically discuss the available data, identify the current gaps and provide key concepts that will help clinicians translate the biology of adipokines in the context of atherosclerosis and cardio-metabolic diseases.
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Affiliation(s)
- M Ruscica
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy
| | - A Baragetti
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy
| | - A L Catapano
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; IRCCS Multimedica Hospital, Sesto San Giovanni, Milan, Italy
| | - G D Norata
- Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Milan, Italy; SISA Center for the Study of Atherosclerosis, Bassini Hospital, Cinisello Balsamo, Italy; School of Biomedical Sciences, Curtin Health Innovation Research Institute, Curtin University, Perth, Western Australia, Australia.
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Yang H, Guo W, Li J, Cao S, Zhang J, Pan J, Wang Z, Wen P, Shi X, Zhang S. Leptin concentration and risk of coronary heart disease and stroke: A systematic review and meta-analysis. PLoS One 2017; 12:e0166360. [PMID: 28278178 PMCID: PMC5344319 DOI: 10.1371/journal.pone.0166360] [Citation(s) in RCA: 44] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2016] [Accepted: 10/27/2016] [Indexed: 11/19/2022] Open
Abstract
Background and purpose Although high leptin concentration has been shown to be correlated with established vascular risk factors, epidemiologic studies have reported inconclusive results on the association between leptin and cardiovascular diseases (CVD). Therefore, a meta-analysis was performed to evaluate this issue. Methods We searched Pubmed, Embase, and the Cochrane Library from their inception to Jan 2016 for both case-control and cohort studies that assessed leptin concentration and CVD risk. Reports with odds ratio (OR), risk ratio (RR) and corresponding 95% confidence intervals (CI) were considered. The data were extracted by two investigators independently. Results A total of 13 epidemiologic studies totaling 4257 CVD patients and 26710 controls were included. A significant inverse association was shown between leptin and coronary heart disease (CHD), with an overall OR of 1.16 (95% CI: 1.02–1.32), but not for stroke (OR = 1.21, 95% CI 0.98–1.48) under sociodemographic adjustment. Further adjustment for additional cardiovascular risk factors resulted in ORs of 1.16 (95% CI 0.97–1.40) for CHD and 1.10 (95% CI 0.89–1.35) for stroke. The findings remained when analyses were restricted to high-quality studies and indicated OR estimates of 1.07 (95% CI 0.96–1.19) for CHD and 0.98 (95% CI 0.76–1.25) for stroke. In a subgroup meta-analysis, a high leptin level was not independently associated with CHD in both females (OR = 1.03, 95% CI 0.86–1.23) and males (OR = 1.09, 95% CI 0.95–1.26) or with stroke in both females (OR = 1.13, 95% CI 0.87–1.47) and males (OR = 0.80, 95% CI 0.59–1.09). There was no significant publication bias as suggested by Egger test outcomes. Conclusions Our findings indicate that high leptin levels may not be associated with risks of CHD and stroke. Further large, well-designed prospective cohort studies are needed to fully evaluate the role of leptin on the risk of CVD.
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Affiliation(s)
- Han Yang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Jie Li
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Shengli Cao
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Jiakai Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Jie Pan
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Zhihui Wang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Peihao Wen
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Xiaoyi Shi
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
| | - Shuijun Zhang
- Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
- Key Laboratory of Hepatobiliary and Pancreatic Surgery & Digestive Organ Transplantation of Henan Province, Henan Province, China
- * E-mail:
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Pawlik A, Teler J, Maciejewska A, Sawczuk M, Safranow K, Dziedziejko V. Adiponectin and leptin gene polymorphisms in women with gestational diabetes mellitus. J Assist Reprod Genet 2017; 34:511-516. [PMID: 28050671 DOI: 10.1007/s10815-016-0866-2] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2016] [Accepted: 12/20/2016] [Indexed: 12/16/2022] Open
Abstract
PURPOSE Gestational diabetes mellitus (GDM) is the glucose intolerance occurring during pregnancy. The prevalence of GDM is increased in obese women. Leptin and adiponectin are adipokines that play an important role in the regulation of insulin secretion and glucose and lipid metabolism. The aim of this study was to examine the association between adiponectin and leptin gene polymorphisms and the development of GDM. METHODS This case-control study included 204 pregnant women with GDM and 207 pregnant women with normal glucose tolerance (NGT). The diagnosis of GDM was based on a 75-g oral glucose tolerance test (OGTT) at 24-28 weeks' gestation. To discriminate the ADIPOQ rs266729, rs1501299 and LEP rs2167270 alleles, TaqMan® Pre-Designed SNP Genotyping Assays were used. RESULTS There was a statistically significant association between the ADIPOQ rs266729 gene polymorphism and GDM. Among women with GDM, a higher prevalence of the G allele was observed (GG and CG genotypes). Multivariate logistic regression analysis, taking into account age, BMI before pregnancy, past pregnancies and the ADIPOQ rs266729 gene polymorphism, revealed that the presence of a G allele is an independent risk factor for GDM. Moreover, there was the association between the LEP rs2167270 polymorphism and the requirement for daily insulin, which was significantly higher in women with the A allele (AA and GA genotypes). CONCLUSIONS The results of our study suggest an association between adiponectin gene rs266729 as well as leptin gene rs2167270 polymorphisms and GDM.
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Affiliation(s)
- Andrzej Pawlik
- Department of Physiology, Pomeranian Medical University, Powstancow Wlkp. 72, 70-111, Szczecin, Poland.
| | - Joanna Teler
- Department of Obstetrics and Gynecology, County Hospital, Zielona Gora, Poland
| | - Agnieszka Maciejewska
- Faculty of Physical Education and Health Promotion, University of Szczecin, Szczecin, Poland
| | - Marek Sawczuk
- Faculty of Physical Education and Health Promotion, University of Szczecin, Szczecin, Poland
| | - Krzysztof Safranow
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
| | - Violetta Dziedziejko
- Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, Szczecin, Poland
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Paz-Filho GJ. Metabolic syndrome in children and teenagers: worth assessing it, but how? ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2017; 61:1-4. [PMID: 28273200 PMCID: PMC10522121 DOI: 10.1590/2359-3997000000249] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Accepted: 01/23/2017] [Indexed: 11/22/2022]
Affiliation(s)
- Gilberto J. Paz-Filho
- John Curtin School of Medical ResearchThe Australian National UniversityCanberraACTAustralia John Curtin School of Medical Research, The Australian National University, Canberra, ACT, Australia
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Kendrick J, Zelnick L, Chonchol M, Siscovick D, Hoofnagle AN, Ix JH, Sarnak M, Shlipak M, Kestenbaum B, de Boer IH. Serum Bicarbonate Is Associated with Heart Failure in the Multi-Ethnic Study of Atherosclerosis. Am J Nephrol 2016; 45:118-126. [PMID: 27941322 PMCID: PMC5296282 DOI: 10.1159/000454783] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 11/05/2016] [Indexed: 11/19/2022]
Abstract
BACKGROUND Low serum bicarbonate concentrations are associated with mortality and kidney disease progression. Data regarding associations between bicarbonate and cardiovascular disease (CVD) are scarce. METHODS We performed a cohort study of 6,229 adult participants from the Multi-Ethnic Study of Atherosclerosis, a community-based cohort free of CVD at baseline. Serum bicarbonate was measured at baseline. Cardiovascular outcomes were defined as: (1) subclinical CVD (left ventricular mass [LVM] and aortic pulse pressure [PP] measured at baseline), (2) incident atherosclerotic cardiovascular events (CVE; composite of myocardial infarction, resuscitated cardiac arrest, stroke, coronary heart disease death, and stroke death), and (3) incident heart failure. RESULTS During a median (interquartile range) follow-up of 8.5 (7.7-8.6) years, 331 (5.3%) participants had an incident CVE and 174 (2.8%) developed incident heart failure. We stratified analyses by use of diuretics because we observed a significant interaction between diuretic use and bicarbonate with study outcomes. Among diuretic nonusers, with adjustment, bicarbonate ≥25 mEq/L was associated with an estimated 3.0 g greater LVM (95% CI 0.5-5.0) and 1.0 mm Hg higher aortic PP (95% CI 0.4-2.0) compared to bicarbonate 23-24 mEq/L. Each 1 mEq/L of bicarbonate increase was associated with a 13% higher risk of incident heart failure (hazards ratio 1.13, 95% CI 1.01-2.11). Among diuretic users, higher bicarbonate was not associated with CVD. Bicarbonate was not associated with incident atherosclerotic CVE irrespective of diuretic use. CONCLUSION Among nonusers of diuretics in a large community-based study, higher serum bicarbonate concentrations are associated with subclinical CVD and new heart failure.
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Affiliation(s)
- Jessica Kendrick
- Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO
- Denver Health Medical Center, Denver, CO
| | - Leila Zelnick
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle WA
| | - Michel Chonchol
- Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO
| | | | | | - Joachim H. Ix
- Division of Nephrology and Hypertension, Department of Medicine, University of California, San Diego, CA
| | - Mark Sarnak
- Division of Nephrology, Tufts Medical Center, Boston, MA
| | - Michael Shlipak
- Division of General Internal Medicine, San Francisco Veterans Affairs Medical Center and University of California, San Francisco, CA
| | - Bryan Kestenbaum
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle WA
| | - Ian H. de Boer
- Division of Nephrology, Kidney Research Institute, University of Washington, Seattle WA
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Gasbarrino K, Mantzoros C, Gorgui J, Veinot JP, Lai C, Daskalopoulou SS. Circulating Chemerin Is Associated With Carotid Plaque Instability, Whereas Resistin Is Related to Cerebrovascular Symptomatology. Arterioscler Thromb Vasc Biol 2016; 36:1670-8. [PMID: 27312219 DOI: 10.1161/atvbaha.115.306741] [Citation(s) in RCA: 31] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2015] [Accepted: 05/23/2016] [Indexed: 01/08/2023]
Abstract
OBJECTIVE The rupture of unstable carotid atherosclerotic plaques is one of the main causes of cerebrovascular ischemic events. There is need for circulating markers that can predict plaque instability and risk of stroke. Proinflammatory chemerin, leptin, and resistin, along with anti-inflammatory adiponectin, are adipokines with direct influence on vascular function. We investigated the association of circulating adipokines with carotid plaque instability and cerebrovascular symptomatology. APPROACH AND RESULTS Neurologically symptomatic and asymptomatic patients (n=165) scheduled for carotid endarterectomy were recruited. Fasting blood samples were collected preoperatively; adiponectin and leptin levels were determined by radioimmunoassay; and chemerin and resistin levels were measured by enzyme-linked immunosorbent assays. The instability of plaque specimens was assessed using gold-standard histological classifications. Chemerin was significantly associated with plaque instability. The fully adjusted model, accounting for age, sex, body mass index, high-sensitivity C-reactive protein, type 2 diabetes mellitus, and circulating adiponectin, leptin, and resistin, yielded an odds ratio of 0.991 (95% confidence interval 0.985-0.998) for plaque instability per unit increase in chemerin. High leptin levels were significantly associated with presence of specific features of plaque instability. In subjects with type 2 diabetes mellitus, resistin levels were significantly elevated in symptomatic when compared with asymptomatic subjects (P=0.001) and increased the risk of cerebrovascular symptomatology (adjusted odds ratio 1.264, 95% confidence interval 1.004-1.594). CONCLUSIONS Low chemerin and high resistin levels were associated with carotid disease severity, suggesting that these adipokines may act as potential markers for plaque instability and stroke risk. Future studies are needed to assess causation between circulating adipokines and plaque instability.
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Affiliation(s)
- Karina Gasbarrino
- From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.)
| | - Christos Mantzoros
- From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.)
| | - Jessica Gorgui
- From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.)
| | - John P Veinot
- From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.)
| | - Chi Lai
- From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.)
| | - Stella S Daskalopoulou
- From the Department of Medicine, Faculty of Medicine, McGill University, Montreal, Quebec, Canada (K.G., J.G., S.S.D.); Department of Internal Medicine, Division of Endocrinology, Diabetes, and Metabolism, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA (C.M.); and Department of Pathology and Laboratory Medicine, University of Ottawa Heart Institute, Ottawa, Ontario, Canada (J.P.V., C.L.).
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Ryan MJ, Coleman TT, Sasser JM, Pittman KM, Hankins MW, Stec DE. Vascular smooth muscle-specific deletion of the leptin receptor attenuates leptin-induced alterations in vascular relaxation. Am J Physiol Regul Integr Comp Physiol 2016; 310:R960-7. [PMID: 26936780 DOI: 10.1152/ajpregu.00336.2015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2015] [Accepted: 02/23/2016] [Indexed: 01/09/2023]
Abstract
Obesity is a risk factor for cardiovascular disease and is associated with increased plasma levels of the adipose-derived hormone leptin. Vascular smooth muscle cells (VSMC) express leptin receptors (LepR); however, their physiological role is unclear. We hypothesized that leptin, at levels to mimic morbid obesity, impairs vascular relaxation. To test this, we used control and VSM-LepR knockout mice (VSM-LepR KO) created with a tamoxifen-inducible specific Cre recombinase to delete the LepR gene in VSMC. Control (10-12 wk old) and VSM-LepR KO (10-12 wk old) mice were fed a diet containing tamoxifen (50 mg/kg) for 6 wk, after which vascular reactivity was studied in isolated carotid arteries using an organ chamber bath. Vessels were incubated with leptin (100 ng/ml) or vehicle (0.1 mM Tris·HCl) for 30 min. Leptin treatment resulted in significant impairment of vessel relaxation to the endothelial-specific agonist acetylcholine (ACh). When these experiments were repeated in the presence of the superoxide scavenger tempol, relaxation responses to ACh were restored. VSM-LepR deletion resulted in a significant attenuation of leptin-mediated impaired ACh-induced relaxation. These data show that leptin directly impairs vascular relaxation via a VSM-LepR-mediated mechanism, suggesting a potential pathogenic role for leptin to increase cardiovascular risk during obesity.
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Affiliation(s)
- Michael J Ryan
- Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, Jackson, Mississippi; and
| | - T Taylor Coleman
- Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, Jackson, Mississippi; and
| | - Jennifer M Sasser
- Department of Pharmacology and Toxicology, University of Mississippi Medical Center, Jackson, Mississippi
| | - Katarina M Pittman
- Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, Jackson, Mississippi; and
| | - Michael W Hankins
- Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, Jackson, Mississippi; and
| | - David E Stec
- Department of Physiology and Biophysics, Mississippi Center for Obesity Research, Cardiovascular-Renal Research Center, Jackson, Mississippi; and
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Bickel C, Schnabel RB, Zeller T, Lackner KJ, Rupprecht HJ, Blankenberg S, Sinning C, Westermann D. Predictors of leptin concentration and association with cardiovascular risk in patients with coronary artery disease: results from the AtheroGene study. Biomarkers 2016; 22:210-218. [PMID: 26769430 DOI: 10.3109/1354750x.2015.1130745] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/20/2023]
Abstract
CONTEXT Leptin is produced in white adipose tissue, but also in human coronary atherosclerotic lesions. OBJECTIVE The aim of this study is to assess the prognostic value of leptin in patients with proven coronary artery disease (CAD) (N = 1907). METHODS AtheroGene is a contemporary CAD cohort study (N = 3229). Median follow-up time was 3.8 (Quartile 1/3 with 2.8/4.9) years. RESULTS Leptin concentration was associated with a hazard ratio (HR) for the fully adjusted model of HR = 1.32 in women but was not significant in men. The endpoint cardiovascular death and non-fatal myocardial infarction was observed in 167 patients. CONCLUSION In women with known CAD, increased leptin concentration is useful for predicting cardiovascular death and non-fatal myocardial infarction.
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Affiliation(s)
- Christoph Bickel
- a Department of Internal Medicine , Federal Armed Forces Central Hospital , Koblenz , Germany
| | - Renate B Schnabel
- b Department of General and Interventional Cardiology , University Heart Center Hamburg , Hamburg , Germany
| | - Tanja Zeller
- b Department of General and Interventional Cardiology , University Heart Center Hamburg , Hamburg , Germany
| | - Karl J Lackner
- c Institute of Clinical Chemistry and Laboratory Medicine, Johannes Gutenberg-University Mainz , Mainz , Germany
| | - Hans J Rupprecht
- d Department of Medicine II , GPR Rüsselsheim , Rüsselsheim , Germany
| | - Stefan Blankenberg
- b Department of General and Interventional Cardiology , University Heart Center Hamburg , Hamburg , Germany
| | - Christoph Sinning
- b Department of General and Interventional Cardiology , University Heart Center Hamburg , Hamburg , Germany
| | - Dirk Westermann
- b Department of General and Interventional Cardiology , University Heart Center Hamburg , Hamburg , Germany
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Saad MI, Abdelkhalek TM, Saleh MM, Kamel MA, Youssef M, Tawfik SH, Dominguez H. Insights into the molecular mechanisms of diabetes-induced endothelial dysfunction: focus on oxidative stress and endothelial progenitor cells. Endocrine 2015; 50:537-67. [PMID: 26271514 DOI: 10.1007/s12020-015-0709-4] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2015] [Accepted: 07/25/2015] [Indexed: 12/13/2022]
Abstract
Diabetes mellitus is a heterogeneous, multifactorial, chronic disease characterized by hyperglycemia owing to insulin insufficiency and insulin resistance (IR). Recent epidemiological studies showed that the diabetes epidemic affects 382 million people worldwide in 2013, and this figure is expected to be 600 million people by 2035. Diabetes is associated with microvascular and macrovascular complications resulting in accelerated endothelial dysfunction (ED), atherosclerosis, and cardiovascular disease (CVD). Unfortunately, the complex pathophysiology of diabetic cardiovascular damage is not fully understood. Therefore, there is a clear need to better understand the molecular pathophysiology of ED in diabetes, and consequently, better treatment options and novel efficacious therapies could be identified. In the light of recent extensive research, we re-investigate the association between diabetes-associated metabolic disturbances (IR, subclinical inflammation, dyslipidemia, hyperglycemia, dysregulated production of adipokines, defective incretin and gut hormones production/action, and oxidative stress) and ED, focusing on oxidative stress and endothelial progenitor cells (EPCs). In addition, we re-emphasize that oxidative stress is the final common pathway that transduces signals from other conditions-either directly or indirectly-leading to ED and CVD.
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Affiliation(s)
- Mohamed I Saad
- Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt.
- Hudson Institute of Medical Research, School of Clinical Sciences, Monash University, Melbourne, VIC, Australia.
| | - Taha M Abdelkhalek
- Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Moustafa M Saleh
- Department of Human Genetics, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Maher A Kamel
- Department of Biochemistry, Medical Research Institute, Alexandria University, Alexandria, Egypt
| | - Mina Youssef
- Department of Human Genetics, McGill University, Montreal, QC, Canada
| | - Shady H Tawfik
- Department of Molecular Medicine, University of Padova, Padua, Italy
| | - Helena Dominguez
- Department of Biomedical Sciences, Copenhagen University, Copenhagen, Denmark
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