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Wang L, Gao P, Gao X. Determinative sleep traits associated with dyslipidemia in obstructive sleep apnea patients. BMC Pulm Med 2025; 25:105. [PMID: 40057676 PMCID: PMC11889753 DOI: 10.1186/s12890-025-03480-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2024] [Accepted: 01/03/2025] [Indexed: 05/13/2025] Open
Abstract
BACKGROUND Obstructive sleep apnea (OSA) is recognized to increase the risk of dyslipidemia; however, the specific sleep traits in OSA that influence dyslipidemia are poorly understood. This study sought to determine which sleep traits are independently associated with dyslipidemia and serum lipid profiles in patients with OSA. METHODS In this cohort study, 5239 participants were included from the Sleep Heart Health Study. Further, OSA was diagnosed via polysomnography with an AHI ≥ 5 events/h. Sleep traits were assessed using polysomnographic data and questionnaires. Then, logistic regression was used to identify sleep traits that predict dyslipidemia in OSA patients. Non-linear associations between sleep traits and dyslipidemia were evaluated using restricted cubic splines. The potential mediating effect of body mass index (BMI) was also calculated. Later, linear regression analysis identified sleep traits that were independently linked to lipid levels. RESULTS After adjusting for confounding factors, logistic regression identified sleep latency (OR: 1.005, 95% CI: 1.002-1.009, P = 0.001), rapid eye movement (REM) stage (OR: 0.987, 95% CI: 0.977-0.998, P = 0.022), REM latency (OR: 1.001, 95% CI: 1.000-1.002, P = 0.027), mean oxygen saturation (meanSpO2) (OR: 0.961, 95% CI: 0.926-0.996, P = 0.031), percentage of time with oxygen saturation below 95% (T95) (OR: 1.003, 95% CI: 1.001-1.005, P = 0.005), and time to fall asleep (OR: 1.004, 95% CI: 1.000-1.007, P = 0.042) as variables independently associated with dyslipidemia. No significant non-linear associations were found (all P >0.05). BMI mediated the association between REM stage, meanSpO2, T95, and dyslipidemia risk. Linear regression analysis identified T95 as a consistent independent determinant of all lipid parameters. Additionally, the meanSpO2 and sleep latency were significant independent determinants of most lipid parameters. CONCLUSIONS Sleep latency, sleep architecture, and nocturnal hypoxemia are key factors in dyslipidemia among patients with OSA. These insights suggest potential biomarkers and targeted interventions for the management of lipid-related complications of OSA.
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Affiliation(s)
- Longlong Wang
- Division I, Department of Geriatric Respiratory, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong Provincial Geriatrics Institute, Guangzhou, China
| | - Ping Gao
- Division I, Department of Geriatric Respiratory, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong Provincial Geriatrics Institute, Guangzhou, China
| | - Xinglin Gao
- Division I, Department of Geriatric Respiratory, Guangdong Provincial People's Hospital, (Guangdong Academy of Medical Sciences), Southern Medical University, Guangdong Provincial Geriatrics Institute, Guangzhou, China.
- Division I, Department of Geriatric Respiratory, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences, Guangdong Provincial Geriatrics Institute), Southern Medical University, No. 106, Zhongshan 2nd Road, Yuexiu District, Guangzhou, China.
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Ding Y, Jiang L, Wang T, Chen Y, Pan Y, Li X, Yan H, Chen W, Zhang G, Wang Y. Oxidised low-density lipoprotein and adverse outcome in patients with acute mild ischaemic stroke or high-risk TIA: a secondary analysis of the INSPIRES randomised clinical trial. Stroke Vasc Neurol 2025:svn-2024-003664. [PMID: 40010751 DOI: 10.1136/svn-2024-003664] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 02/14/2025] [Indexed: 02/28/2025] Open
Abstract
BACKGROUND Research data regarding the correlation between elevated oxidised low-density lipoprotein (oxLDL) cholesterol concentrations and unfavourable clinical outcomes in individuals experiencing minor acute ischaemic cerebrovascular events or transient ischaemic attack (TIA) with presumed atherosclerotic aetiology are still limited. METHODS This investigation incorporated a cohort of 5814 participants derived from the Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis clinical trial. The core laboratory conducted blinded measurements of baseline plasma oxLDL concentrations. Multivariable Cox regression analyses were employed to assess the correlations between oxLDL levels and adverse clinical events. The principal endpoint for efficacy assessment was defined as the occurrence of stroke within a 90-day follow-up period. Additional secondary endpoints encompassed composite vascular events during the same observation window. The main safety endpoint assessed was the occurrence of bleeding events of moderate to severe intensity. RESULTS The final analytical cohort comprised 5814 patients included in the final analysis. The mean age was 63.7±9.6 years, and 36.0% were female. The average concentration of circulating oxLDL was 36.62 µg/dL. Elevated oxLDL concentrations demonstrated a potential correlation with heightened stroke risk (T3 vs T1: HR 1.39, 95% CI 1.04 to 1.85), ischaemic stroke (T3 vs T1: HR 1.31, 95% CI 0.98 to 1.76) and composite vascular events (T3 vs T1: HR 1.36, 95% CI 1.02 to 1.81) within 90 days. An increased concentration of oxLDL demonstrated a significant association with elevated susceptibility to moderate and severe haemorrhagic events (T3 vs T1: HR 3.61, 95% CI 1.26 to 10.34) within 90 days. CONCLUSION Increased concentrations of oxLDL demonstrated an independent correlation with both stroke recurrence and the occurrence of moderate-to-severe haemorrhagic events in individuals presenting with acute minor ischaemic stroke or TIA at elevated risk, accompanied by intracranial or extracranial atherosclerotic lesions.
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Affiliation(s)
- Yaowei Ding
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Lingling Jiang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Tingting Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yuxin Chen
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yuesong Pan
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Xiaotong Li
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Hongyi Yan
- China National Clinical Research Center for Neurological Diseases, Beijing, China
| | - Weiqi Chen
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Guojun Zhang
- Department of Clinical Diagnosis, Laboratory of Beijing Tiantan Hospital, Capital Medical University, Beijing, China
| | - Yilong Wang
- Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
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Bakillah A, Al Subaiee M, Soliman AF, Obeid KK, Bashir SF, Al Hussaini A, Al Arab M, Al Otaibi A, Mubarak SAS, Al Qarni AA. Plasma Atrial Natriuretic Peptide Predicts Oxidized Low-Density Lipoprotein Levels in Type 2 Diabetes Mellitus Patients Independent of Circulating Adipokine and Cytokine. Int J Mol Sci 2025; 26:1859. [PMID: 40076485 PMCID: PMC11899485 DOI: 10.3390/ijms26051859] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2025] [Revised: 02/09/2025] [Accepted: 02/19/2025] [Indexed: 03/14/2025] Open
Abstract
Atrial natriuretic peptide (ANP) and oxidized low-density lipoprotein (ox-LDL) play essential roles in the development and progression of vascular complications associated with type 2 diabetes mellitus (T2DM), and both are independently linked to cardiovascular diseases (CVD). However, the relationship between ANP and ox-LDL in patients with T2DM remains unclear as previous studies have primarily focused on circulating levels in various diseases. This study investigated the relationship between ANP and ox-LDL levels in obese individuals with T2DM. The cohort included 57 patients with T2DM (mean age 61.14 ± 9.99 years; HbA1c 8.66 ± 1.60%; BMI 35.15 ± 6.65 kg/m2). Notably, 95% of the patients had hypertension, 82% had dyslipidemia, 59% had an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2, 14% had coronary artery disease (CAD), and 5% had a history of stroke. Plasma concentrations of ANP and ox-LDL were measured using ELISA. Adipokines and cytokines levels were measured using the multiplex® MAP Human Adipokine Magnetic Beads Spearman's correlation analysis which revealed a negative correlation between ANP and ox-LDL (r = -0.446, p = 0.001) as well as with the ox-LDL/apoB ratio (r = -0.423, p = 0.001) and ox-LDL/LDLc ratio (r = -0.307, p = 0.038). Multivariable regression analysis indicated that ANP was independently associated with ox-LDL (β = -115.736, p = 0.005). Stepwise linear regression further identified TNFα, leptin, and adiponectin as the strongest predictors influencing the relationship between ANP and ox-LDL levels (β = -64.664, p = 0.0311, and r2 = 0.546 for the model). However, these factors did not significantly mediate this association. This study emphasizes the need for further exploration of the complex interaction between ANP and ox-LDL in larger patient populations. This could provide valuable insights into potential therapeutic approaches for managing vascular complications in obese individuals with T2DM.
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Affiliation(s)
- Ahmed Bakillah
- King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Mubarraz 36428, Saudi Arabia; (S.F.B.); (A.A.H.); (M.A.A.); (A.A.O.); (S.A.S.M.); (A.A.A.Q.)
- Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Mubarraz 36428, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Maram Al Subaiee
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Ayman Farouk Soliman
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Khamis Khamees Obeid
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Shahinaz Faisal Bashir
- King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Mubarraz 36428, Saudi Arabia; (S.F.B.); (A.A.H.); (M.A.A.); (A.A.O.); (S.A.S.M.); (A.A.A.Q.)
- Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Mubarraz 36428, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Arwa Al Hussaini
- King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Mubarraz 36428, Saudi Arabia; (S.F.B.); (A.A.H.); (M.A.A.); (A.A.O.); (S.A.S.M.); (A.A.A.Q.)
- Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Mubarraz 36428, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Mohammad Al Arab
- King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Mubarraz 36428, Saudi Arabia; (S.F.B.); (A.A.H.); (M.A.A.); (A.A.O.); (S.A.S.M.); (A.A.A.Q.)
- Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Mubarraz 36428, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Abeer Al Otaibi
- King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Mubarraz 36428, Saudi Arabia; (S.F.B.); (A.A.H.); (M.A.A.); (A.A.O.); (S.A.S.M.); (A.A.A.Q.)
- Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Mubarraz 36428, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Sindiyan Al Shaikh Mubarak
- King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Mubarraz 36428, Saudi Arabia; (S.F.B.); (A.A.H.); (M.A.A.); (A.A.O.); (S.A.S.M.); (A.A.A.Q.)
- Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Mubarraz 36428, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
| | - Ali Ahmed Al Qarni
- King Abdullah International Medical Research Center (KAIMRC), Eastern Region, Al Mubarraz 36428, Saudi Arabia; (S.F.B.); (A.A.H.); (M.A.A.); (A.A.O.); (S.A.S.M.); (A.A.A.Q.)
- Division of Biomedical Research Core Facility, King Saud bin Abdulaziz University for Health Sciences (KSAU-HS), Al Mubarraz 36428, Saudi Arabia
- Ministry of National Guard-Health Affairs (MNGHA), King Abdulaziz Hospital, Al Mubarraz 36428, Saudi Arabia; (M.A.S.); (A.F.S.); (K.K.O.)
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de Girolamo G, Andreassen OA, Bauer M, Brambilla P, Calza S, Citerà N, Corcoy R, Fagiolini A, Garcia-Argibay M, Godin O, Klingler F, Kobayashi NF, Larsson H, Leboyer M, Matura S, Martinelli A, De la Peña-Arteaga V, Poli R, Reif A, Ritter P, Rødevand LN, Magno M, Caselani E. Medical comorbidities in bipolar disorder (BIPCOM): clinical validation of risk factors and biomarkers to improve prevention and treatment. Study protocol. Int J Bipolar Disord 2024; 12:15. [PMID: 38703295 PMCID: PMC11069492 DOI: 10.1186/s40345-024-00337-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Accepted: 04/24/2024] [Indexed: 05/06/2024] Open
Abstract
BACKGROUND BIPCOM aims to (1) identify medical comorbidities in people with bipolar disorder (BD); (2) examine risk factors and clinical profiles of Medical Comorbidities (MC) in this clinical group, with a special focus on Metabolic Syndrome (MetS); (3) develop a Clinical Support Tool (CST) for the personalized management of BD and medical comorbidities. METHODS The BIPCOM project aims to investigate MC, specifically MetS, in individuals with BD using various approaches. Initially, prevalence rates, characteristics, genetic and non-genetic risk factors, and the natural progression of MetS among individuals with BD will be assessed by analysing Nordic registers, biobanks, and existing patient datasets from 11 European recruiting centres across 5 countries. Subsequently, a clinical study involving 400 participants from these sites will be conducted to examine the clinical profiles and incidence of specific MetS risk factors over 1 year. Baseline assessments, 1-year follow-ups, biomarker analyses, and physical activity measurements with wearable biosensors, and focus groups will be performed. Using this comprehensive data, a CST will be developed to enhance the prevention, early detection, and personalized treatment of MC in BD, by incorporating clinical, biological, sex and genetic information. This protocol will highlight the study's methodology. DISCUSSION BIPCOM's data collection will pave the way for tailored treatment and prevention approaches for individuals with BD. This approach has the potential to generate significant healthcare savings by preventing complications, hospitalizations, and emergency visits related to comorbidities and cardiovascular risks in BD. BIPCOM's data collection will enhance BD patient care through personalized strategies, resulting in improved quality of life and reduced costly interventions. The findings of the study will contribute to a better understanding of the relationship between medical comorbidities and BD, enabling accurate prediction and effective management of MetS and cardiovascular diseases. TRIAL REGISTRATION ISRCTN68010602 at https://www.isrctn.com/ISRCTN68010602 . Registration date: 18/04/2023.
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Affiliation(s)
- Giovanni de Girolamo
- Unit of Epidemiological and Evaluation Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy.
| | - Ole A Andreassen
- Norwegian Center for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway
| | - Michael Bauer
- Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany
| | - Paolo Brambilla
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Stefano Calza
- Department of Molecular and Translational Medicine, University of Brescia, Brescia, Italy
| | - Nicholas Citerà
- Department of Neurosciences and Mental Health, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Rosa Corcoy
- Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain
| | - Andrea Fagiolini
- Department of Molecular and Developmental Medicine, Division of Psychiatry, University of Siena School of Medicine, Siena, Italy
| | - Miguel Garcia-Argibay
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Ophélia Godin
- Fondation FondaMental, Créteil, France
- Univ Paris Est Créteil, INSERM U955, IMRB, Translational NeuroPsychiatry Laboratory, Créteil, France
| | - Florian Klingler
- Deutsche Gesellschaft Für Bipolare Störungen (DGBS) E.V, Hamburg, Germany
| | - Nene F Kobayashi
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Henrik Larsson
- School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden
| | - Marion Leboyer
- Fondation FondaMental, Créteil, France
- Fédération Hospitalo-Universitaire de Médecine de Précision en Psychiatrie (FHU ADAPT), Créteil, France
| | - Silke Matura
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Alessandra Martinelli
- Unit of Epidemiological and Evaluation Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Víctor De la Peña-Arteaga
- Institut de Recerca Sant Pau (IR SANT PAU), Barcelona, Spain
- CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), 28029, Madrid, Spain
| | - Roberto Poli
- Department of Mental Health, Psychiatric Unit of Cremona General Hospital, Azienda Ospedaliera di Cremona, Cremona, Italy
| | - Andreas Reif
- Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, Goethe University Frankfurt, University Hospital, Frankfurt am Main, Germany
| | - Philipp Ritter
- Department of Psychiatry and Psychotherapy, Universitätsklinikum Carl Gustav Carus an der Technischen Universität Dresden, Dresden, Germany
| | - Linn N Rødevand
- Norwegian Center for Mental Disorders Research (NORMENT), Division of Mental Health and Addiction, Institute of Clinical Medicine, Oslo University Hospital, University of Oslo, Oslo, Norway
| | - Marta Magno
- Unit of Epidemiological and Evaluation Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
| | - Elisa Caselani
- Unit of Epidemiological and Evaluation Psychiatry, IRCCS Istituto Centro San Giovanni di Dio Fatebenefratelli, Brescia, Italy
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Saarinen HJ, Lahtela J, Mähönen P, Palomäki A. The association between inflammation, arterial stiffness, oxidized LDL and cardiovascular disease in Finnish men with metabolic syndrome - a 15-year follow-up study. BMC Cardiovasc Disord 2024; 24:162. [PMID: 38491429 PMCID: PMC10941448 DOI: 10.1186/s12872-024-03818-x] [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: 01/01/2024] [Accepted: 02/27/2024] [Indexed: 03/18/2024] Open
Abstract
BACKGROUND All-cause mortality and cardiovascular disease are increased in subjects with metabolic syndrome (MetS). Risk scores are used to predict individual risk of heart disease. We performed a long-term follow-up study to investigate whether risk scores and cardiovascular risk factors such as arterial stiffness, high-sensitive C-reactive protein (hs-CRP) and oxidized LDL (OxLDL) can be used to predict cardiovascular events in Finnish men with MetS. METHODS After baseline measurements we followed 105 Finnish men aged 30 to 65 years with MetS for a mean period of 16.4 years. The primary outcome of the study was a composite of myocardial infarction, stroke, symptomatic vascular disease diagnosed with invasive angiography, coronary or peripheral revascularization, amputation due to peripheral vascular disease, cardiovascular death and non-cardiovascular death. The endpoints were retrieved from electronic medical records. RESULTS The number of acute myocardial infarctions and strokes during the first 10 years was lower than estimated by FINRISK score but SCORE predicted cardiovascular death correctly. During the whole follow-up period, 27 of 105 participants (25.8%) had 30 endpoint events. The incidence of the primary composite outcome was significantly lower in subjects with hs-CRP < 1.0 mg/L than in subjects with hs-CRP ≥ 1.0 mg/L (6 of 41 subjects [14.6%] vs. 21 of 64 subjects [32.8%]; p = 0.036). The incidence of the primary composite outcome was higher among subjects with large artery elasticity classified as borderline compared to subjects with normal large artery elasticity (5 of 10 subjects [50%] vs. 22 of 93 subjects [24%]; p = 0.05). There was no difference in the incidence of primary composite outcome in groups with different degrees of small artery elasticity or different level of oxLDL. CONCLUSIONS Men with MetS who had hs-CRP ≥ 1.0 mg/L had higher risk for CVD and all-cause mortality than those with hs-CRP of < 1.0 mg/L. This also applies to subjects with borderline decreased large artery elasticity. The amount of OxLDL had no predictive value on the incidence of CVD and all-cause mortality. Men with MetS participating in the Hämeenlinna Metabolic Syndrome Research Program without lifestyle or drug intervention had better outcome for myocardial infarction or stroke than estimated by the FINRISK score. TRIAL REGISTRATION ClinicalTrials.gov NCT01119404 retrospectively registered 07/05/2010.
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Affiliation(s)
| | - Jorma Lahtela
- Tampere University Central Hospital, Teiskontie 35, Tampere, FI-33521, Finland
| | - Päivi Mähönen
- Vita Laboratories, Laivakatu 5 F, Helsinki, FI-00150, Finland
- Department of Bacteriology & Immunology, University of Helsinki, Yliopistonkatu 4, Helsinki, FI-00100, Finland
| | - Ari Palomäki
- Department of Emergency Medicine, Kanta-Häme Central Hospital, Ahvenistontie 20, Hämeenlinna, FI-13530, Finland
- Cardiometabolic Unit, Linnan Klinikka, Raatihuoneenkatu 10, Hämeenlinna, FI-13100, Finland
- Faculty of Medicine and Health Technology, Tampere University, Tampereen Yliopisto, FI-33014, Finland
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Engin A. Endothelial Dysfunction in Obesity and Therapeutic Targets. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:489-538. [PMID: 39287863 DOI: 10.1007/978-3-031-63657-8_17] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Parallel to the increasing prevalence of obesity in the world, the mortality from cardiovascular disease has also increased. Low-grade chronic inflammation in obesity disrupts vascular homeostasis, and the dysregulation of adipocyte-derived endocrine and paracrine effects contributes to endothelial dysfunction. Besides the adipose tissue inflammation, decreased nitric oxide (NO)-bioavailability, insulin resistance (IR), and oxidized low-density lipoproteins (oxLDLs) are the main factors contributing to endothelial dysfunction in obesity and the development of cardiorenal metabolic syndrome. While normal healthy perivascular adipose tissue (PVAT) ensures the dilation of blood vessels, obesity-associated PVAT leads to a change in the profile of the released adipo-cytokines, resulting in a decreased vasorelaxing effect. Higher stiffness parameter β, increased oxidative stress, upregulation of pro-inflammatory cytokines, and nicotinamide adenine dinucleotide phosphate (NADP) oxidase in PVAT turn the macrophages into pro-atherogenic phenotypes by oxLDL-induced adipocyte-derived exosome-macrophage crosstalk and contribute to the endothelial dysfunction. In clinical practice, carotid ultrasound, higher leptin levels correlate with irisin over-secretion by human visceral and subcutaneous adipose tissues, and remnant cholesterol (RC) levels predict atherosclerotic disease in obesity. As a novel therapeutic strategy for cardiovascular protection, liraglutide improves vascular dysfunction by modulating a cyclic adenosine monophosphate (cAMP)-independent protein kinase A (PKA)-AMP-activated protein kinase (AMPK) pathway in PVAT in obese individuals. Because the renin-angiotensin-aldosterone system (RAAS) activity, hyperinsulinemia, and the resultant IR play key roles in the progression of cardiovascular disease in obesity, RAAS-targeted therapies contribute to improving endothelial dysfunction. By contrast, arginase reciprocally inhibits NO formation and promotes oxidative stress. Thus, targeting arginase activity as a key mediator in endothelial dysfunction has therapeutic potential in obesity-related vascular comorbidities. Obesity-related endothelial dysfunction plays a pivotal role in the progression of type 2 diabetes (T2D). The peroxisome proliferator-activated receptor gamma (PPARγ) agonist, rosiglitazone (thiazolidinedione), is a popular drug for treating diabetes; however, it leads to increased cardiovascular risk. Selective sodium-glucose co-transporter-2 (SGLT-2) inhibitor empagliflozin (EMPA) significantly improves endothelial dysfunction and mortality occurring through redox-dependent mechanisms. Although endothelial dysfunction and oxidative stress are alleviated by either metformin or EMPA, currently used drugs to treat obesity-related diabetes neither possess the same anti-inflammatory potential nor simultaneously target endothelial cell dysfunction and obesity equally. While therapeutic interventions with glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide or bariatric surgery reverse regenerative cell exhaustion, support vascular repair mechanisms, and improve cardiometabolic risk in individuals with T2D and obesity, the GLP-1 analog exendin-4 attenuates endothelial endoplasmic reticulum stress.
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Affiliation(s)
- Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey.
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey.
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Zhang Q, Du G, Tong L, Guo X, Wei Y. Overexpression of LOX-1 in hepatocytes protects vascular smooth muscle cells from phenotype transformation and wire injury induced carotid neoatherosclerosis through ALOX15. Biochim Biophys Acta Mol Basis Dis 2023; 1869:166805. [PMID: 37468019 DOI: 10.1016/j.bbadis.2023.166805] [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: 10/30/2022] [Revised: 06/16/2023] [Accepted: 07/06/2023] [Indexed: 07/21/2023]
Abstract
Neoatherosclerosis (NA), the main pathological basis of late stent failure, is the main limitation of interventional therapy. However, the specific pathogenesis and treatment remain unclear. In vivo, NA model was established by carotid wire injury and high-fat feeding in ApoE-/- mice. Oxidized low-density lipoprotein receptor-1/lectin-like oxidized low-density lipoprotein receptor-1 (OLR1/LOX-1), a specific receptor for oxidized low-density lipoprotein (ox-LDL), was specifically ectopically overexpressed in hepatocytes by portal vein injection of adeno-associated serotype 8 (AAV8)-thyroid binding globulin (TBG)-Olr1 and the protective effect against NA was examined. In vitro, LOX-1 was overexpressed on HHL5 using lentivirus (LV)-OLR1 and the vascular smooth muscle cells (VSMCs)-HHL5 indirect co-culture system was established to examine its protective effect on VSMCs and the molecular mechanism. Functionally, we found that specific ectopic overexpression of LOX-1 by hepatocytes competitively engulfed and metabolized ox-LDL, alleviating its resulting phenotypic transformation of VSMCs including migration, downregulation of contractile shape markers (smooth muscle α-actin (SMαA) and smooth muscle-22α (SM22α)), and upregulation of proliferative/migratory shape markers (osteopontin (OPN) and Vimentin) as well as foaminess and apoptosis, thereby alleviating NA, which independent of low-density lipoprotein (LDL) lowering treatment (evolocumab, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9)). Mechanistically, we found that overexpression of LOX-1 in hepatocytes competitively engulfed and metabolized ox-LDL through upregulation of arachidonate-15-lipoxygenase (ALOX15), which further upregulated scavenger receptor class B type I (SRBI) and ATP-binding cassette transporter A1 (ABCA1). In conclusion, the overexpression of LOX-1 in liver protects VSMCs from phenotypic transformation and wire injury induced carotid neoatherosclerosis through ALOX15.
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Affiliation(s)
- Qing Zhang
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Gaohui Du
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Lu Tong
- Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Xiaopeng Guo
- Department of Radiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
| | - Yumiao Wei
- Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Key Laboratory of Biological Targeted Therapy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Hubei Provincial Engineering Research Center of Immunological Diagnosis and Therapy for Cardiovascular Diseases, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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8
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Vekic J, Stromsnes K, Mazzalai S, Zeljkovic A, Rizzo M, Gambini J. Oxidative Stress, Atherogenic Dyslipidemia, and Cardiovascular Risk. Biomedicines 2023; 11:2897. [PMID: 38001900 PMCID: PMC10669174 DOI: 10.3390/biomedicines11112897] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 10/20/2023] [Accepted: 10/23/2023] [Indexed: 11/26/2023] Open
Abstract
Oxidative stress is the consequence of an overproduction of reactive oxygen species (ROS) that exceeds the antioxidant defense mechanisms. Increased levels of ROS contribute to the development of cardiovascular disorders through oxidative damage to macromolecules, particularly by oxidation of plasma lipoproteins. One of the most prominent features of atherogenic dyslipidemia is plasma accumulation of small dense LDL (sdLDL) particles, characterized by an increased susceptibility to oxidation. Indeed, a considerable and diverse body of evidence from animal models and epidemiological studies was generated supporting oxidative modification of sdLDL particles as the earliest event in atherogenesis. Lipid peroxidation of LDL particles results in the formation of various bioactive species that contribute to the atherosclerotic process through different pathophysiological mechanisms, including foam cell formation, direct detrimental effects, and receptor-mediated activation of pro-inflammatory signaling pathways. In this paper, we will discuss recent data on the pathophysiological role of oxidative stress and atherogenic dyslipidemia and their interplay in the development of atherosclerosis. In addition, a special focus will be placed on the clinical applicability of novel, promising biomarkers of these processes.
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Affiliation(s)
- Jelena Vekic
- Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia; (J.V.); (A.Z.)
| | - Kristine Stromsnes
- Department of Physiology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain; (K.S.); (S.M.); (J.G.)
| | - Stefania Mazzalai
- Department of Physiology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain; (K.S.); (S.M.); (J.G.)
| | - Aleksandra Zeljkovic
- Department of Medical Biochemistry, University of Belgrade-Faculty of Pharmacy, 11000 Belgrade, Serbia; (J.V.); (A.Z.)
| | - Manfredi Rizzo
- Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, University of Palermo, 90100 Palermo, Italy
| | - Juan Gambini
- Department of Physiology, Faculty of Medicine, University of Valencia, 46010 Valencia, Spain; (K.S.); (S.M.); (J.G.)
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9
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Ben-Assayag H, Brzezinski RY, Berliner S, Zeltser D, Shapira I, Rogowski O, Toker S, Eldor R, Shenhar-Tsarfaty S. Transitioning from having no metabolic abnormality nor obesity to metabolic impairment in a cohort of apparently healthy adults. Cardiovasc Diabetol 2023; 22:226. [PMID: 37633936 PMCID: PMC10463945 DOI: 10.1186/s12933-023-01954-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 08/08/2023] [Indexed: 08/28/2023] Open
Abstract
INTRODUCTION The global prevalence of metabolic syndrome and its association with increased morbidity and mortality has been rigorously studied. However, the true prevalence of "metabolic health", i.e. individuals without any metabolic abnormalities is not clear. Here, we sought to determine the prevalence of "metabolically healthy" individuals and characterize the "transition phase" from metabolic health to development of dysfunction over a follow-up period of 5 years. METHODS We included 20,507 individuals from the Tel Aviv Sourasky Medical Center Inflammation Survey (TAMCIS) which comprises apparently healthy individuals attending their annual health survey. A second follow-up visit was documented after 4.8 (± 0.6) years. We defined a group of metabolically healthy participants without metabolic abnormalities nor obesity and compared their characteristics and change in biomarkers over time to participants who developed metabolic impairment on their follow-up visit. The intersections of all metabolic syndrome components and elevated high sensitivity C-reactive protein (hs-CRP) were also analyzed. RESULTS A quarter of the cohort (5379 individuals, (26.2%) did not fulfill any metabolic syndrome criteria during their baseline visit. A total of 985 individuals (12.7% of returning participants) developed metabolic criteria over time with hypertension being the most prevalent component to develop among these participants. Individuals that became metabolically impaired over time demonstrated increased overlap between metabolic syndrome criteria and elevated hs-CRP levels. The group that became metabolically impaired over time also presented higher delta values of WBC, RBC, liver biomarkers, and uric acid compared with participants who were consistently metabolically impaired. LDL-C (low-density lipoprotein cholesterol) delta levels were similar. CONCLUSIONS Roughly one-quarter of apparently healthy adults are defined as "metabolically healthy" according to current definitions. The transition from health to metabolic dysfunction is accompanied with active inflammation and several non-metabolic syndrome biomarkers. Aggressive screening for these biomarkers, blood pressure and hs-CRP might help identify apparently healthy individuals at increased risk of developing metabolic syndrome over time.
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Affiliation(s)
- Hadas Ben-Assayag
- Department of Internal Medicine "C", "D" & "E", Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239, Tel Aviv, Israel
- Affiliated with Sackler Faculty of Medicine, The Tel Aviv University, Tel Aviv, Israel
| | - Rafael Y Brzezinski
- Department of Internal Medicine "C", "D" & "E", Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239, Tel Aviv, Israel
- Affiliated with Sackler Faculty of Medicine, The Tel Aviv University, Tel Aviv, Israel
| | - Shlomo Berliner
- Department of Internal Medicine "C", "D" & "E", Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239, Tel Aviv, Israel
- Affiliated with Sackler Faculty of Medicine, The Tel Aviv University, Tel Aviv, Israel
| | - David Zeltser
- Department of Emergency Medicine, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Itzhak Shapira
- Department of Internal Medicine "C", "D" & "E", Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239, Tel Aviv, Israel
- Affiliated with Sackler Faculty of Medicine, The Tel Aviv University, Tel Aviv, Israel
| | - Ori Rogowski
- Department of Internal Medicine "C", "D" & "E", Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239, Tel Aviv, Israel
- Affiliated with Sackler Faculty of Medicine, The Tel Aviv University, Tel Aviv, Israel
| | - Sharon Toker
- Coller School of Management, Tel Aviv University, Tel Aviv, Israel
| | - Roy Eldor
- Affiliated with Sackler Faculty of Medicine, The Tel Aviv University, Tel Aviv, Israel
- Diabetes Unit, Institute of Endocrinology, Metabolism and Hypertension, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
| | - Shani Shenhar-Tsarfaty
- Department of Internal Medicine "C", "D" & "E", Tel Aviv Sourasky Medical Center, 6 Weizmann Street, 64239, Tel Aviv, Israel.
- Affiliated with Sackler Faculty of Medicine, The Tel Aviv University, Tel Aviv, Israel.
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10
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Mirolyubova O, Kholmatova K, Postoeva A, Kostrova G, Malyutina S, Kudryavtsev AV. Socio-Demographic, Lifestyle, and Cardiometabolic Characteristics Associated with Low-Grade Systemic Inflammation in Russian Adult Population. Biomolecules 2023; 13:biom13050835. [PMID: 37238705 DOI: 10.3390/biom13050835] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 05/08/2023] [Accepted: 05/10/2023] [Indexed: 05/28/2023] Open
Abstract
Mortality from cardiovascular diseases (CVDs) is higher in Russia compared to other European countries. High-sensitivity C-reactive protein (hs-CRP) is a biomarker of inflammation, and its elevated levels indicate increased CVD risks. We aim to describe the prevalence of low-grade systemic inflammation (LGSI) and the associated factors in a Russian population. The Know Your Heart cross-sectional study was conducted in Arkhangelsk, Russia in 2015-2017 with a population sample aged 35-69 years (n = 2380). LGSI was defined as hs-CRP ≥ 2 and <10 mg/L, and its associations with socio-demographic, lifestyle, and cardiometabolic characteristics were analyzed. The prevalence of LGSI (age-standardized to European Standard Population 2013) was 34.1% (33.5% in men and 36.1% in women). In the total sample, the increased odds ratios (ORs) of LGSI were associated with abdominal obesity (2.1), smoking (1.9), dyslipidemia (1.5), pulmonary diseases (1.4), and hypertension (1.3); the decreased ORs were in women (0.6) and in married participants (0.6). In men, the ORs were higher with abdominal obesity (2.1), smoking (2.0), CVDs (1.5), and hazardous drinking (1.5); in women-with abdominal obesity (4.4) and pulmonary diseases (1.5). In conclusion, one-third of the adult population in Arkhangelsk had LGSI. Abdominal obesity was the strongest LGSI correlate in both sexes, while the profiles of other associated factors were different between men and women.
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Affiliation(s)
- Olga Mirolyubova
- Department of Faculty Therapy, Northern State Medical University, Arkhangelsk 163069, Russia
| | - Kamila Kholmatova
- International Research Competence Centre, Northern State Medical University, Arkhangelsk 163069, Russia
- Department of Hospital Therapy and Endocrinology, Northern State Medical University, Arkhangelsk 163069, Russia
- Department of Community Medicine, UiT the Arctic University of Norway, N-9037 Tromsø, Norway
| | - Anna Postoeva
- Department of Hospital Therapy and Endocrinology, Northern State Medical University, Arkhangelsk 163069, Russia
| | - Galina Kostrova
- Department of Normal Physiology, Northern State Medical University, Arkhangelsk 163069, Russia
| | - Sofia Malyutina
- Research Institute of Internal and Preventive Medicine, Branch of Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk 630008, Russia
- Department of Therapy, Hematology and Transfusiology, Novosibirsk State Medical University, Novosibirsk 630091, Russia
| | - Alexander V Kudryavtsev
- International Research Competence Centre, Northern State Medical University, Arkhangelsk 163069, Russia
- Department of Community Medicine, UiT the Arctic University of Norway, N-9037 Tromsø, Norway
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11
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Wang S, Han Y, Zhao H, Han X, Yin Y, Wu J, Zhang Y, Zeng X. Association between Coffee Consumption, Caffeine Intake, and Metabolic Syndrome Severity in Patients with Self-Reported Rheumatoid Arthritis: National Health and Nutrition Examination Survey 2003-2018. Nutrients 2022; 15:nu15010107. [PMID: 36615765 PMCID: PMC9824592 DOI: 10.3390/nu15010107] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 12/19/2022] [Accepted: 12/21/2022] [Indexed: 12/28/2022] Open
Abstract
Rheumatoid arthritis (RA) is chronic inflammatory disease. Although coffee impacts metabolism, no evidence has shown an association between coffee consumption and decreased risk for developing metabolic syndrome (MetS) among RA patients. Hence, we examined the association between coffee consumption and metabolic syndrome severity among 1094 participants with self-reported RA. Accordingly, patients with MetS z-scores of <0 and ≥0 were designated as low- and high-risk groups, respectively. In the fully adjusted model, drinking over two cups of coffee daily was associated with a decrease in the MetS z-score (p = 0.04). Subgroup analysis showed that in the low-risk group, daily intake of <2 cups of coffee was associated with low MetS z-scores (p = 0.003), scores (p = 0.03). Coffee intake was associated with low body mass index (p = 0.03 for 0−2 cups per day; p = 0.02 for >2 cups per day) and low HOMA-IR (β, −2.62; 95%CI, −5.13 to −0.11; p = 0.04). Our study suggests that coffee, but not decaffeinated coffee consumption and total caffeine intake, is associated with MetS severity in RA.
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12
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Jehanathan N, Kapuruge EP, Rogers SP, Williams S, Chung Y, Borges CR. Oxidized LDL is stable in human serum under extended thawed-state conditions ranging from -20 °C to room temperature. J Mass Spectrom Adv Clin Lab 2022; 27:18-23. [PMID: 36578466 PMCID: PMC9791165 DOI: 10.1016/j.jmsacl.2022.12.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Revised: 12/04/2022] [Accepted: 12/06/2022] [Indexed: 12/13/2022] Open
Abstract
Introduction Oxidized LDL (oxLDL) is formed by the spontaneous reaction between aldehyde byproducts of lipid peroxidation and lysine residues of apolipoprotein B within LDL. Clinically, oxLDL is used as a marker of coronary artery disease and predictor of metabolic syndrome risk. Despite its popularity as a clinical marker, no systematic studies of oxLDL stability, in which serum or plasma has been pre-analytically exposed to an array of different time and temperature conditions, have been carried out. Objective To systematically evaluate the stability of oxLDL in human serum samples exposed to thawed conditions (> -30 °C) for varying periods of time while monitoring a second protein/small molecule redox system as a positive control for non-enzymatic biomolecular activity. Methods OxLDL was measured in serum samples, from 24 different humans, that had been pre-exposed to three different time courses at 23 °C, 4 °C and -20 °C using ELISA kits from Mercodia that employ the 4E6 mouse monoclonal antibody. A liquid chromatography/mass spectrometry-based marker of serum exposure to thawed conditions known as ΔS-Cys-Albumin was employed as a positive control. Results OxLDL was stable in serum exposed to 23 °C for up to 48 h, 4 °C for 21 days, or -20 °C for 65 days. ΔS-Cys-Albumin changed dramatically during these time courses (p < 0.001). Conclusions OxLDL is remarkably stable ex vivo in human serum samples exposed to thawed conditions.
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Affiliation(s)
- Nilojan Jehanathan
- School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, United States,The Biodesign Institute at Arizona State University, Tempe, AZ 85287, United States
| | - Erandi P. Kapuruge
- School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, United States,The Biodesign Institute at Arizona State University, Tempe, AZ 85287, United States
| | - Stephen P. Rogers
- The Biodesign Institute at Arizona State University, Tempe, AZ 85287, United States
| | - Stacy Williams
- The Biodesign Institute at Arizona State University, Tempe, AZ 85287, United States
| | - Yunro Chung
- The Biodesign Institute at Arizona State University, Tempe, AZ 85287, United States,College of Health Solutions, Arizona State University, Phoenix, AZ 85004, United States
| | - Chad R. Borges
- School of Molecular Sciences, Arizona State University, Tempe, AZ 85287, United States,The Biodesign Institute at Arizona State University, Tempe, AZ 85287, United States,Corresponding author at: The Biodesign Institute at Arizona State University, P.O. Box 876401, Tempe, AZ 85287, United States.
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13
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Istomin N, Härma MA, Akhi R, Nissinen AE, Savolainen MJ, Adeshara K, Lehto M, Groop PH, Koivukangas V, Hukkanen J, Hörkkö S. Total fecal IgA levels increase and natural IgM antibodies decrease after gastric bypass surgery. APMIS 2022; 130:637-646. [PMID: 35959517 PMCID: PMC9805076 DOI: 10.1111/apm.13268] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2022] [Accepted: 08/09/2022] [Indexed: 01/10/2023]
Abstract
Obesity is associated with low-grade inflammation and increased systemic oxidative stress. Roux-en-Y gastric bypass (RYGB) surgery is known to ameliorate the obesity-induced metabolic dysfunctions. We aimed to study the levels of natural antibodies in feces, before and 6 months after RYGB surgery in obese individuals with and without type 2 diabetes (T2D). Sixteen individuals with T2D and 14 non-diabetic (ND) individuals were operated. Total IgA, IgG and IgM antibody levels and specific antibodies to oxidized low-density lipoprotein (oxLDL), malondialdehyde-acetaldehyde adducts (MAA adducts), Porphyromonas gingivalis gingipain A hemagglutinin domain (Rgp44) and phosphocholine (PCho) were measured using chemiluminescence immunoassay. Total fecal IgA was elevated, while total IgM and IgG were not affected by the surgery. Fecal natural IgM specific to oxLDL decreased significantly in both T2D and ND individuals, while fecal IgM to Rgp44 and PCho decreased significantly in T2D individuals. A decrease in IgG to MAA-LDL, Rgp44 and PCho was detected. RYGB surgery increases the levels of total fecal IgA and decreases fecal natural IgG and IgM antibodies specific to oxLDL. Natural antibodies and IgA are important in maintaining the normal gut homeostasis and first-line defense against microbes, and their production is markedly altered with RYGB surgery.
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Affiliation(s)
- Natalie Istomin
- Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Nordlab, Oulu University Hospital, Oulu, Finland
| | - Mari-Anne Härma
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Ramin Akhi
- Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
| | - Antti E Nissinen
- Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland
| | - Markku J Savolainen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Research Unit of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Krishna Adeshara
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Markku Lehto
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Per-Henrik Groop
- Folkhälsan Institute of Genetics, Folkhälsan Research Center, Helsinki, Finland.,Abdominal Center, Nephrology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.,Clinical and Molecular Metabolism, Faculty of Medicine Research Programs, University of Helsinki, Helsinki, Finland
| | - Vesa Koivukangas
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Department of Surgery, Oulu University Hospital, Oulu, Finland
| | - Janne Hukkanen
- Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland.,Research Unit of Internal Medicine and Biocenter Oulu, University of Oulu, Oulu, Finland
| | - Sohvi Hörkkö
- Medical Microbiology and Immunology, Research Unit of Biomedicine, University of Oulu, Oulu, Finland.,Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
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14
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Rosuvastatin and co-enzyme Q10 improve high-fat and high-fructose diet-induced metabolic syndrome in rats via ameliorating inflammatory and oxidative burden. Biomed Pharmacother 2022; 153:113526. [PMID: 36076607 DOI: 10.1016/j.biopha.2022.113526] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2022] [Revised: 08/04/2022] [Accepted: 08/08/2022] [Indexed: 11/17/2022] Open
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15
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Su W, Liu G, Mohajer B, Wang J, Shen A, Zhang W, Liu B, Guermazi A, Gao P, Cao X, Demehri S, Wan M. Senescent preosteoclast secretome promotes metabolic syndrome associated osteoarthritis through cyclooxygenase 2. eLife 2022; 11:e79773. [PMID: 35881544 PMCID: PMC9365389 DOI: 10.7554/elife.79773] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Accepted: 05/06/2022] [Indexed: 01/10/2023] Open
Abstract
Background Metabolic syndrome-associated osteoarthritis (MetS-OA) is a distinct osteoarthritis phenotype defined by the coexistence of MetS or its individual components. Despite the high prevalence of MetS-OA, its pathogenic mechanisms are unclear. The aim of this study was to determine the role of cellular senescence in the development of MetS-OA. Methods Analysis of the human osteoarthritis initiative (OAI) dataset was conducted to investigate the MRI subchondral bone features of MetS-human OA participants. Joint phenotype and senescent cells were evaluated in two MetS-OA mouse models: high-fat diet (HFD)-challenged mice and STR/Ort mice. In addition, the molecular mechanisms by which preosteoclasts become senescent as well as how the senescent preosteoclasts impair subchondral bone microenvironment were characterized using in vitro preosteoclast culture system. Results Humans and mice with MetS are more likely to develop osteoarthritis-related subchondral bone alterations than those without MetS. MetS-OA mice exhibited a rapid increase in joint subchondral bone plate and trabecular thickness before articular cartilage degeneration. Subchondral preosteoclasts undergo senescence at the pre- or early-osteoarthritis stage and acquire a unique secretome to stimulate osteoblast differentiation and inhibit osteoclast differentiation. Antagonizing preosteoclast senescence markedly mitigates pathological subchondral alterations and osteoarthritis progression in MetS-OA mice. At the molecular level, preosteoclast secretome activates COX2-PGE2, resulting in stimulated differentiation of osteoblast progenitors for subchondral bone formation. Administration of a selective COX2 inhibitor attenuated subchondral bone alteration and osteoarthritis progression in MetS-OA mice. Longitudinal analyses of the human Osteoarthritis Initiative (OAI) cohort dataset also revealed that COX2 inhibitor use, relative to non-selective nonsteroidal antiinflammatory drug use, is associated with less progression of osteoarthritis and subchondral bone marrow lesion worsening in participants with MetS-OA. Conclusions Our findings suggest a central role of a senescent preosteoclast secretome-COX2/PGE2 axis in the pathogenesis of MetS-OA, in which selective COX2 inhibitors may have disease-modifying potential. Funding This work was supported by the National Institutes of Health grant R01AG068226 and R01AG072090 to MW, R01AR079620 to SD, and P01AG066603 to XC.
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Affiliation(s)
- Weiping Su
- Department of Orthopaedic Surgery, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
- Department of Orthopaedic Surgery, The Third Xiangya Hospital of Central South UniversityChangshaChina
| | - Guanqiao Liu
- Department of Orthopaedic Surgery, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
- Division of Orthopaedics & Traumatology, Department of Orthopaedics, Southern Medical University Nanfang HospitalGuangzhouChina
| | - Bahram Mohajer
- Musculoskeletal Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Jiekang Wang
- Department of Orthopaedic Surgery, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Alena Shen
- University of Southern California, Dornsife College of Letters, Arts and SciencesLos AngelesUnited States
| | - Weixin Zhang
- Department of Orthopaedic Surgery, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Bin Liu
- Department of Orthopaedic Surgery, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Ali Guermazi
- Department of Radiology, Boston University School of MedicineBostonUnited States
| | - Peisong Gao
- Johns Hopkins Asthma & Allergy Center, Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Xu Cao
- Department of Orthopaedic Surgery, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Shadpour Demehri
- Musculoskeletal Radiology, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
| | - Mei Wan
- Department of Orthopaedic Surgery, Russell H. Morgan Department of Radiology and Radiological Science, The Johns Hopkins University School of MedicineBaltimoreUnited States
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Otelea MR, Nartea R, Popescu FG, Covaleov A, Mitoiu BI, Nica AS. The Pathological Links between Adiposity and the Carpal Tunnel Syndrome. Curr Issues Mol Biol 2022; 44:2646-2663. [PMID: 35735622 PMCID: PMC9221759 DOI: 10.3390/cimb44060181] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Revised: 06/01/2022] [Accepted: 06/06/2022] [Indexed: 11/16/2022] Open
Abstract
An association between obesity and carpal tunnel syndrome is found in many epidemiological studies. Therefore, there is a need to evaluate the physiopathological links that could explain the association between these two entities. Ectopic adipose tissue is responsible for metabolic syndrome and inflammation, and is a major risk factor for diabetes and cardiovascular diseases. Taking these elements into consideration, we conducted an extensive literature revision of the subject, considering as ectopic fat-related mechanisms the following: (a) the direct compression and the association with the metabolic syndrome of the fat deposition around the wrist, (b) the insulin resistance, dyslipidemia, inflammatory, and oxidative mechanisms related to the central deposition of the fat, (c) the impaired muscle contraction and metabolism related to myosteatosis. Each section presents the cellular pathways which are modified by the ectopic deposition of the adipose tissue and the impact in the pathogeny of the carpal tunnel syndrome. In conclusion, the experimental and clinical data support the epidemiological findings. Efforts to reduce the obesity epidemics will improve not only cardio-metabolic health but will reduce the burden of the disability-free life expectancy due to the carpal tunnel syndrome.
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Affiliation(s)
- Marina Ruxandra Otelea
- Clinical Department 5, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania;
| | - Roxana Nartea
- Clinical Department 9, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (A.C.); (B.I.M.); (A.S.N.)
- National Institute for Rehabilitation, Physical Medicine and Balneoclimatology, 030079 Bucharest, Romania
- Correspondence:
| | - Florina Georgeta Popescu
- Department V, Internal Medicine, Victor Babeş University of Medicine and Pharmacy, 300041 Timisoara, Romania;
- Emergency Municipal Hospital, 300254 Timisoara, Romania
| | - Anatoli Covaleov
- Clinical Department 9, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (A.C.); (B.I.M.); (A.S.N.)
| | - Brindusa Ilinca Mitoiu
- Clinical Department 9, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (A.C.); (B.I.M.); (A.S.N.)
| | - Adriana Sarah Nica
- Clinical Department 9, Carol Davila University of Medicine and Pharmacy, 050474 Bucharest, Romania; (A.C.); (B.I.M.); (A.S.N.)
- National Institute for Rehabilitation, Physical Medicine and Balneoclimatology, 030079 Bucharest, Romania
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17
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Salvio G, Ciarloni A, Cutini M, delli Muti N, Finocchi F, Perrone M, Rossi S, Balercia G. Metabolic Syndrome and Male Fertility: Beyond Heart Consequences of a Complex Cardiometabolic Endocrinopathy. Int J Mol Sci 2022; 23:5497. [PMID: 35628307 PMCID: PMC9143238 DOI: 10.3390/ijms23105497] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/02/2022] [Accepted: 05/13/2022] [Indexed: 12/06/2022] Open
Abstract
Metabolic syndrome (MetS) is a highly prevalent condition among adult males, affecting up to 41% of men in Europe. It is characterized by the association of obesity, hypertension, and atherogenic dyslipidemia, which lead to premature morbidity and mortality due to cardiovascular disease (CVD). Male infertility is another common condition which accounts for about 50% of cases of couple infertility worldwide. Interestingly, male infertility and MetS shares several risk factors (e.g., smoking, ageing, physical inactivity, and excessive alcohol consumption), leading to reactive oxygen species (ROS) production and increased oxidative stress (OS), and resulting in endothelial dysfunction and altered semen quality. Thus, the present narrative review aims to discuss the pathophysiological mechanisms which link male infertility and MetS and to investigate the latest available evidence on the reproductive consequences of MetS.
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Affiliation(s)
| | | | | | | | | | | | | | - Giancarlo Balercia
- Division of Endocrinology, Department of Clinical and Molecular Sciences (DISCLIMO), Polytechnic University of Marche, 60126 Ancona, Italy; (G.S.); (A.C.); (M.C.); (N.d.M.); (F.F.); (M.P.); (S.R.)
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Lyu J, Fukunaga K, Imachi H, Sato S, Kobayashi T, Saheki T, Ibata T, Yoshimura T, Iwama H, Murao K. Oxidized LDL Downregulates ABCA1 Expression via MEK/ERK/LXR Pathway in INS-1 Cells. Nutrients 2021; 13:nu13093017. [PMID: 34578896 PMCID: PMC8465850 DOI: 10.3390/nu13093017] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Revised: 08/23/2021] [Accepted: 08/24/2021] [Indexed: 12/23/2022] Open
Abstract
Impaired insulin secretion is one of the main causes of type 2 diabetes. Cholesterol accumulation-induced lipotoxicity contributes to impaired insulin secretion in pancreatic beta cells. However, the detailed mechanism in this process remains unclear. In this study, we proved that oxidized low-density lipoprotein (OxLDL) reduced insulin content, decreased PDX-1 expression, and impaired glucose-stimulated insulin secretion (GSIS) in INS-1 cells, which were rescued by addition of high-density lipoprotein (HDL). OxLDL receptors and cholesterol content were increased by OxLDL. Consistently, OxLDL suppressed cholesterol transporter ABCA1 expression and transcription in a dose-dependent and time-dependent manner. Inhibition of MEK by its specific inhibitor, PD98059, altered the effect of OxLDL on ABCA1 transcription and activation of ERK. Next, chromatin immunoprecipitation assay demonstrated that liver X receptor (LXR) could directly bind to ABCA1 promoter and this binding was inhibited by OxLDL. Furthermore, OxLDL decreased the nuclear LXR expression, which was prevented by HDL. LXR-enhanced ABCA1 transcription was suppressed by OxLDL, and the effect was cancelled by mutation of the LXR-binding sites. In summary, our study shows that OxLDL down-regulates ABCA1 expression by MEK/ERK/LXR pathway, leading to cholesterol accumulation in INS-1 cells, which may result in impaired insulin synthesis and GSIS.
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Affiliation(s)
- Jingya Lyu
- Department of Physiology, School of Medicine, Jinan University, 601 Huangpu Avenue West, Tianhe District, Guangzhou 510632, China;
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
| | - Kensaku Fukunaga
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
| | - Hitomi Imachi
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
| | - Seisuke Sato
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
| | - Toshihiro Kobayashi
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
| | - Takanobu Saheki
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
| | - Tomohiro Ibata
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
| | - Takafumi Yoshimura
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
| | - Hisakazu Iwama
- Life Science Research Center, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan;
| | - Koji Murao
- Department of Endocrinology and Metabolism, Faculty of Medicine, Kagawa University, 1750-1, Miki-cho, Kita-gun, Kagawa 761-0793, Japan; (K.F.); (H.I.); (S.S.); (T.K.); (T.S.); (T.I.); (T.Y.)
- Correspondence:
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20
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Wang S. Association between serum low-density lipoprotein cholesterol and metabolic syndrome in a working population. Lipids Health Dis 2021; 20:73. [PMID: 34275455 PMCID: PMC8286618 DOI: 10.1186/s12944-021-01500-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 07/08/2021] [Indexed: 11/16/2022] Open
Abstract
Background The studies, investigating the association of low-density lipoprotein cholesterol (LDL-C) with metabolic syndrome (MetS) are limited with controversial conclusions. Therefore, this study aimed at revealing the specific relationship between the serum LDL-C levels and MetS prevalence in a large working population. Methods Secondary data analysis of a cross-sectional study, conducted between 2012 and 2016 in Spain on participants aged within the range of 20–70 years, involved 60,799 workers. Logistic regression analysis was applied to evaluate the association between the levels of serum LDL-C and MetS prevalence. Results Among the 60,799 workers, the prevalence of MetS was 9.0%. The odds ratios (95% confidence intervals) of MetS prevalence were 1.27 (1.16–1.39) and 1.53 (1.41–1.65) for the individuals with the LDL-C levels in lower (< 103.8 mg/dL) and upper (> 135.8 mg/dL) tertiles as compared to those with the LDL-C levels in middle tertile (103.8–135.8 mg/dL) in the studied population. Similarly, a U-shaped relationship was also observed in male cohort. The serum LDL-C levels associated with the lowest risk of current MetS were 113.6 mg/dL and 117.6 mg/dL in the overall studied population and male cohort, respectively. The female workers with the levels of LDL-C higher than 135.0 mg/dL had an increased prevalence of MetS (P < 0.05). Conclusions The low and high levels of serum LDL-C were associated with an increased prevalence of MetS in the working population and in male workers. Only the high (> 135.0 mg/dL) levels of LDL-C increased MetS prevalence in female workers.
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Affiliation(s)
- Saibin Wang
- Department of Respiratory Medicine, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua Municipal Central Hospital, No. 365, East Renmin Road, Jinhua, 321000, Zhejiang Province, China.
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21
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Chandra NC. A comprehensive account of insulin and LDL receptor activity over the years: A highlight on their signaling and functional role. J Biochem Mol Toxicol 2021; 35:e22840. [PMID: 34227185 DOI: 10.1002/jbt.22840] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 05/13/2021] [Accepted: 06/25/2021] [Indexed: 11/08/2022]
Abstract
Insulin receptor (IR) was discovered in 1970. Shortcomings in IR transcribed signals were found pro-diabetic, which could also inter-relate obesity and atherosclerosis in a time-dependent manner. Low-density lipoprotein receptor (LDLR) was discovered in 1974. Later studies showed that insulin could modulate LDLR expression and activity. Repression of LDLR transcription in the absence or inactivity of insulin showed a direct cause of atherosclerosis. Leptin receptor (OB-R) was found in 1995 and its resistance became responsible for developing obesity. The three interlinked pathologies namely, diabetes, atherosclerosis, and obesity were later on marked as metabolic syndrome-X (MSX). In 2012, the IR-LDLR inter-association was identified. In 2019, the proficiency of signal transmission from this IR-LDLR receptor complex was reported. LDLR was found to mimic IR-generated signaling path when it remains bound to IR in IR-DLR interlocked state. This was the first time LDLR was found sending messages besides its LDL-clearing activity from blood vessels.
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Affiliation(s)
- Nimai C Chandra
- Department of Biochemistry, All India Institute of Medical Sciences, Patna, India
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22
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Cao X, Wu QJ, Chang Q, Zhang TN, Li XS, Chen YX, Zhao YH. Knowledge Mapping of Dietary Factors of Metabolic Syndrome Research: Hotspots, Knowledge Structure, and Theme Trends. Front Nutr 2021; 8:655533. [PMID: 34136515 PMCID: PMC8200392 DOI: 10.3389/fnut.2021.655533] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2021] [Accepted: 05/11/2021] [Indexed: 01/10/2023] Open
Abstract
Background: The global incidence of metabolic syndrome (MetS) is continuously increasing, making it a potential worldwide public health concern. Research on dietary factors related to MetS has attracted considerable attention in the recent decades. However, the research hotspots, knowledge structure, and theme trends for the dietary factors associated with MetS remain unknown, and have not yet been systematically mapped. This study aimed to review the research status of diet as a risk factor for MetS through bibliometric methods. Bibliometric analysis was conducted using the Web of Science database. Research hotspots were identified using biclustering analysis with the gCLUTO software, and knowledge structure was explored via social network analysis using the Ucinet software. Theme trends were investigated using evolutionary analysis with the SciMAT software. In total, 1,305 papers were analyzed. The research output on the dietary factors associated with MetS increased steadily. The research scope was gradually expanding and diverse. Overall, eight research hot spots, four key dietary nodes, and four motor themes on the dietary factors associated with MetS were identified. Fatty acids, dietary fiber, and polyphenols have been the focus of research in this field over the years. Evolutionary analysis showed that fish oil and vitamin C were well-developed research foci recently. Prebiotics was recognized as an emerging theme with certain developmental potential. These findings provide a better understanding of the research status of the dietary factors associated with MetS and a reference for future investigations.
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Affiliation(s)
- Xia Cao
- Department of Library, Shengjing Hospital of China Medical University, Shenyang, China.,Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qi-Jun Wu
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Qing Chang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
| | - Tie-Ning Zhang
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China.,Department of Pediatrics, Pediatric Intensive Care Unit, Shengjing Hospital of China Medical University, Shenyang, China
| | - Xiang-Sen Li
- Department of Library, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yun-Xiang Chen
- Department of Library, Shengjing Hospital of China Medical University, Shenyang, China
| | - Yu-Hong Zhao
- Department of Clinical Epidemiology, Shengjing Hospital of China Medical University, Shenyang, China
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23
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Varghese DS, Ali BR. Pathological Crosstalk Between Oxidized LDL and ER Stress in Human Diseases: A Comprehensive Review. Front Cell Dev Biol 2021; 9:674103. [PMID: 34124059 PMCID: PMC8187772 DOI: 10.3389/fcell.2021.674103] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2021] [Accepted: 04/26/2021] [Indexed: 02/05/2023] Open
Abstract
The oxidative modification of the major cholesterol carrying lipoprotein, oxLDL, is a biomarker as well as a pathological factor in cardiovascular diseases (CVD), type 2 diabetes mellitus (T2DM), obesity and other metabolic diseases. Perturbed cellular homeostasis due to physiological, pathological and pharmacological factors hinder the proper functioning of the endoplasmic reticulum (ER), which is the major hub for protein folding and processing, lipid biosynthesis and calcium storage, thereby leading to ER stress. The cellular response to ER stress is marked by a defensive mechanism called unfolded protein response (UPR), wherein the cell adapts strategies that favor survival. Under conditions of excessive ER stress, when the survival mechanisms fail to restore balance, UPR switches to apoptosis and eliminates the defective cells. ER stress is a major hallmark in metabolic syndromes such as diabetes, non-alcoholic fatty liver disease (NAFLD), neurological and cardiovascular diseases. Though the pathological link between oxLDL and ER stress in cardiovascular diseases is well-documented, its involvement in other diseases is still largely unexplored. This review provides a deep insight into the common mechanisms in the pathogenicity of diseases involving oxLDL and ER stress as key players. In addition, the potential therapeutic intervention of the targets implicated in the pathogenic processes are also explored.
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Affiliation(s)
- Divya Saro Varghese
- Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Bassam R. Ali
- Department of Genetics and Genomics, College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
- Zayed Bin Sultan Center for Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates
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24
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Gkouskou K, Vasilogiannakopoulou T, Andreakos E, Davanos N, Gazouli M, Sanoudou D, Eliopoulos AG. COVID-19 enters the expanding network of apolipoprotein E4-related pathologies. Redox Biol 2021; 41:101938. [PMID: 33730676 PMCID: PMC7943392 DOI: 10.1016/j.redox.2021.101938] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2020] [Revised: 02/12/2021] [Accepted: 03/05/2021] [Indexed: 12/18/2022] Open
Abstract
COVID-19 incidence and case fatality rates (CFR) differ among ethnicities, stimulating efforts to pinpoint genetic factors that could explain these phenomena. In this regard, the multiallelic apolipoprotein E (APOE) gene has recently been interrogated in the UK biobank cohort, demonstrating associations of the APOE ε4/ε4 genotype with COVID-19 severity and mortality. The frequency of the ε4 allele and thus the distribution of APOE ε4/ε4 genotype may differ among populations. We have assessed APOE genotypes in 1638 Greek individuals, based on haplotypes derived from SNP rs7412 and rs429358 and found reduced frequency of ε4/ε4 compared to the British cohort. Herein we discuss this finding in relation to CFR and hypothesize on the potential mechanisms linking APOE ε4/ε4 to severe COVID-19. We postulate that the metabolic deregulation ensued by APOE4, manifested by elevated cholesterol and oxidized lipoprotein levels, may be central to heightened pneumocyte susceptibility to infection and to exaggerated lung inflammation associated with the ε4/ε4 genotype. We also discuss putative dietary and pharmacological approaches for the prevention and management of COVID-19 in APOE ε4/ε4 individuals.
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Affiliation(s)
- Kalliopi Gkouskou
- Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Embiodiagnostics Biology Research Company, Heraklion, Crete, Greece.
| | | | | | | | - Maria Gazouli
- Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Despina Sanoudou
- Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Clinical Genomics and Pharmacogenomics Unit, 4th Department of Internal Medicine, School of Medicine, National and Kapodistrian University of Athens, Greece; Center for New Biotechnologies and Precision Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece
| | - Aristides G Eliopoulos
- Department of Biology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece; Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Center for New Biotechnologies and Precision Medicine, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
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25
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Piceatannol inhibits pyroptosis and suppresses oxLDL-induced lipid storage in macrophages by regulating miR-200a/Nrf2/GSDMD axis. Biosci Rep 2021; 40:226337. [PMID: 32886103 PMCID: PMC7494992 DOI: 10.1042/bsr20201366] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2020] [Revised: 09/01/2020] [Accepted: 09/03/2020] [Indexed: 02/07/2023] Open
Abstract
As a major bioactive compound from grapes, piceatannol (PIC) has been reported to exert anti-atherosclerotic activity in various studies. Nevertheless, the mechanism underlying the effect of piceatannol against atherosclerosis (AS) is elusive. Our study identified miR-200a/Nrf2/GSDMD signaling pathway as critical mediators in the effect of piceatannol on macrophages. In the present study, we confirmed that treatment of piceatannol repressed the oxLDL-induced lipid storage in macrophages. Compared with control group, piceatannol inhibited TG storage and the activity of caspase1. It is noting that in response to oxLDL challenge, piceatannol abated the pyroptosis in RAW264.7 cells, with a decreased expression of caspase1, gasdermin D (GSDMD), IL-18, IL-1β and NLRP3. Moreover, we investigated the role of microRNA (miR)-200a/Nrf2 signaling pathway in the effect of piceatannol. The results declared that after transfection of si-miR-200a or si-Nrf2 plasmids, the effects of piceatannol on macrophages were converted, including lipid storage and pyroptosis. Importantly, si-miR-200a plasmid reduced the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), indicating that miR-200a acted as an enhancer of Nrf2 in macrophages. Collectively, our findings demonstrate that piceatannol exerts anti-atherosclerotic activity on RAW264.7 cells by regulating miR-200a/Nrf2/GSDMD signaling. The present study is the first time to identify miR-200a as a candidate target in AS and declared an association between miR-200a and pyroptosis, which provides a novel therapy for the treatment of AS.
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26
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Fang F, Nuyt AM, Garofalo C, Zhang J, Julien P, Fraser W, Levy E, Luo ZC. Oxidized LDL, insulin sensitivity and beta-cell function in newborns. BMJ Open Diabetes Res Care 2021; 9:9/1/e001435. [PMID: 33687921 PMCID: PMC7944989 DOI: 10.1136/bmjdrc-2020-001435] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Revised: 12/01/2020] [Accepted: 01/09/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Oxidized low-density lipoprotein (OxLDL), a biomarker of oxidative stress, itself possesses proatherogenic and proinflammatory effects. Elevated circulating OxLDL levels have been consistently associated with insulin resistance and diabetes in adults. We sought to assess whether OxLDL may be associated with insulin sensitivity and beta-cell function in early life. RESEARCH DESIGN AND METHODS In a birth cohort study, we assessed cord plasma OxLDL concentration and OxLDL to total LDL ratio in relation to glucose to insulin ratio (an indicator of fetal insulin sensitivity), proinsulin to insulin ratio (an indicator of fetal beta-cell function), and leptin and adiponectin concentrations in 248 singleton newborns. RESULTS Cord plasma OxLDL concentration was positively correlated with glucose to insulin ratio (r=0.24, p<0.001) and proinsulin to insulin ratio (r=0.20, p<0.001) and was not correlated with leptin or adiponectin. Adjusting for maternal and neonatal characteristics, each log unit increase in cord plasma OxLDL concentration was associated with a 25.8% (95% CI 12.8% to 40.3%) increase in glucose to insulin ratio and a 19.0% (95% CI 6.8% to 32.9%) increase in proinsulin to insulin ratio, respectively. Similar associations were observed for cord plasma OxLDL to LDL ratio in relation to cord plasma glucose to insulin ratio and proinsulin to insulin ratio. CONCLUSIONS Higher OxLDL levels were associated with lower fetal beta-cell function (higher proinsulin to insulin ratio) but higher insulin sensitivity (higher glucose to insulin ratio). The study is the first to demonstrate that OxLDL may affect glucose metabolic health in early life in humans.
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Affiliation(s)
- Fang Fang
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Department of Pediatrics, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
- Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Prosserman Center for Population Health Research, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
| | - Anne Monique Nuyt
- Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Québec, Canada
| | - Carole Garofalo
- Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Québec, Canada
| | - Jun Zhang
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Department of Pediatrics, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
| | - Pierre Julien
- Department of Medicine, Molecular and Oncologic Endocrinology and Human Genomics Research Center, CHU-Quebec Laval University Research Center, Laval University, Quebec City, Quebec, Canada
| | - William Fraser
- Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Québec, Canada
- Department of Obstetrics and Gynecology, University of Sherbrooke, Sherbrooke, Quebec, Canada
| | - Emile Levy
- Sainte-Justine University Hospital and Research Center, University of Montreal, Montreal, Québec, Canada
| | - Zhong-Cheng Luo
- Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Department of Pediatrics, Xinhua Hospital, Shanghai Jiao-Tong University School of Medicine, Shanghai, China
- Department of Obstetrics and Gynecology, Lunenfeld-Tanenbaum Research Institute, Prosserman Center for Population Health Research, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
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27
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A Three-Month Consumption of Eggs Enriched with ω-3, ω-5 and ω-7 Polyunsaturated Fatty Acids Significantly Decreases the Waist Circumference of Subjects at Risk of Developing Metabolic Syndrome: A Double-Blind Randomized Controlled Trial. Nutrients 2021; 13:nu13020663. [PMID: 33670720 PMCID: PMC7923083 DOI: 10.3390/nu13020663] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2021] [Revised: 02/10/2021] [Accepted: 02/16/2021] [Indexed: 02/01/2023] Open
Abstract
Alpha-linolenic acid (ALA), docosahexaenoic acid (DHA), rumenic acid (RmA), and punicic acid (PunA) are claimed to influence several physiological functions including insulin sensitivity, lipid metabolism and inflammatory processes. In this double-blind randomized controlled trial, we investigated the combined effect of ALA, DHA, RmA and PunA on subjects at risk of developing metabolic syndrome. Twenty-four women and men were randomly assigned to two groups. Each day, they consumed two eggs enriched with oleic acid (control group) or enriched with ALA, DHA, RmA, and PunA (test group) for 3 months. The waist circumference decreased significantly (−3.17 cm; p < 0.001) in the test group. There were no major changes in plasma insulin and blood glucose in the two groups. The dietary treatments had no significant effect on endothelial function as measured by peripheral arterial tonometry, although erythrocyte nitrosylated hemoglobin concentrations tended to decrease. The high consumption of eggs induced significant elevations in plasma low-density lipoprotein (LDL)- and high-density lipoprotein (HDL)-cholesterol (p < 0.001), which did not result in any change in the LDL/HDL ratio in both groups. These results indicate that consumption of eggs enriched with ALA, DHA, RmA and PunA resulted in favorable changes in abdominal obesity without affecting other factors of the metabolic syndrome.
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Biomarkers of cardiometabolic complications in survivors of childhood acute lymphoblastic leukemia. Sci Rep 2020; 10:21507. [PMID: 33299020 PMCID: PMC7726154 DOI: 10.1038/s41598-020-78493-x] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Accepted: 10/12/2020] [Indexed: 12/14/2022] Open
Abstract
Survivors of childhood acute lymphoblastic leukemia (cALL) are at higher risk of developing cardiometabolic complications. We aimed at exploring the associations between biomarkers of inflammation, oxidative stress, endothelial function, endotoxemia and cardiometabolic risk factors. We conducted a cross-sectional analysis in 246 cALL survivors (mean age, 22.1 ± 6.3 years; mean time since diagnosis, 15.5 ± 5.2 years) and evaluated the associations using a series of logistic regressions. Using structural equation models, we also tested if the relationship between endotoxemia and cardiometabolic complications was mediated by the latent (unobserved) variable inflammation inferred from the observed biomarkers CRP, TNF-α and IL-6. High leptin-adiponectin ratio was associated with obesity [adjusted OR = 15.7; 95% CI (6.2–39.7)], insulin resistance [20.6 (5.2–82.1)] and the metabolic syndrome [11.2 (2.6–48.7)]. Higher levels of plasminogen activator inhibitor-1 and tumor necrosis factor-α were associated with obesity [3.37 (1.6–7.1) and 2.34 (1.3–4.2), respectively] whereas high C-reactive protein levels were associated with insulin resistance [3.3 (1.6–6.8)], dyslipidemia [2.6 (1.4–4.9)] and MetS [6.5 (2.4–17.9)]. Our analyses provided evidence for a directional relationship between lipopolysaccharide binding protein, related to metabolic endotoxemia, inflammation and cardiometabolic outcomes. Identification of biomarkers and biological mechanisms could open new avenues for prevention strategies to minimize the long-term sequelae, improve follow-up and optimize the quality of life of this high-risk population.
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Vatner SF, Zhang J, Oydanich M, Berkman T, Naftalovich R, Vatner DE. Healthful aging mediated by inhibition of oxidative stress. Ageing Res Rev 2020; 64:101194. [PMID: 33091597 PMCID: PMC7710569 DOI: 10.1016/j.arr.2020.101194] [Citation(s) in RCA: 124] [Impact Index Per Article: 24.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2020] [Revised: 09/29/2020] [Accepted: 10/12/2020] [Indexed: 12/14/2022]
Abstract
The progressive increase in lifespan over the past century carries with it some adversity related to the accompanying burden of debilitating diseases prevalent in the older population. This review focuses on oxidative stress as a major mechanism limiting longevity in general, and healthful aging, in particular. Accordingly, the first goal of this review is to discuss the role of oxidative stress in limiting longevity, and compare healthful aging and its mechanisms in different longevity models. Secondly, we discuss common signaling pathways involved in protection against oxidative stress in aging and in the associated diseases of aging, e.g., neurological, cardiovascular and metabolic diseases, and cancer. Much of the literature has focused on murine models of longevity, which will be discussed first, followed by a comparison with human models of longevity and their relationship to oxidative stress protection. Finally, we discuss the extent to which the different longevity models exhibit the healthful aging features through physiological protective mechanisms related to exercise tolerance and increased β-adrenergic signaling and also protection against diabetes and other metabolic diseases, obesity, cancer, neurological diseases, aging-induced cardiomyopathy, cardiac stress and osteoporosis.
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Affiliation(s)
- Stephen F Vatner
- Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Newark, New Jersey, USA.
| | - Jie Zhang
- Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Newark, New Jersey, USA
| | - Marko Oydanich
- Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Newark, New Jersey, USA
| | - Tolga Berkman
- Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Newark, New Jersey, USA
| | - Rotem Naftalovich
- Department of Anesthesiology, New Jersey Medical School, Newark, New Jersey, USA
| | - Dorothy E Vatner
- Department of Cell Biology and Molecular Medicine, New Jersey Medical School, Newark, New Jersey, USA.
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Thomas MM, Zaki ME, Youness E, Hamed K, Khedr AA, Abd El-Massieh PM, Abdo SM, El-Bassyouni HT. Measurement of Serum Chemerin, Oxidized LDL, and Vitamin D Levels in Prader–Willi Syndrome: A Cross-Sectional Study in Pediatric Egyptian Patients. JOURNAL OF CHILD SCIENCE 2020. [DOI: 10.1055/s-0040-1718896] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/23/2022]
Abstract
AbstractPrader–Willi syndrome (PWS) is the commonest genetic cause of obesity. Oxidative stress and chronic low-grade inflammation play a crucial role in the pathogenesis of obesity. Alterations of vitamin D (25-OHD) levels are commonly encountered with obesity. The aim of this study was to analyze serum chemerin, oxidized low-density lipoprotein (ox-LDL), and 25-OHD values in pediatric PWS patients in comparison with obese healthy children and nonobese control groups, highlighting possible correlations with body mass index (BMI) and obesity. Twenty-six PWS Egyptian patients and 26 obese healthy individuals referred to the outpatient clinic of the Clinical Genetics Department, National Research Centre, Cairo, Egypt, and 20 control patients with matching age and sex were enrolled in the study. Patients were clinically diagnosed and confirmed by routine cytogenetic and fluorescence in-situ hybridization analysis. Anthropometric measurements were performed, and BMI was calculated by weight/height2 (kg/m2), and BMI z score was also determined. Serum chemerin, ox-LDL, and vitamin D were determined by enzyme-linked immunosorbent assay. Chemerin levels, which reflected chronic inflammation, were significantly elevated as compared with obese and nonobese controls (p ≤ 0.0001). Concerning oxidative damage, children with PWS showed higher Ox-LDL levels compared with obese and nonobese controls (p < 0.0001). Vitamin D levels were significantly lower in PWS patients compared with obese and nonobese controls (p ≤ 0.0001). Our data showed that obesity in PWS is associated with oxidative stress and chronic low-grade inflammation. Ox-LDL is a good indicator of oxidative stress, and chemerin could be used as a biomarker for the chronic inflammatory state. Furthermore, vitamin D supplementation is recommended in PWS patients
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Affiliation(s)
- Manal M. Thomas
- Clinical Genetics Department, Center of Scientific Excellence, National Research Centre, Cairo, Egypt
| | - Moushira E. Zaki
- Department of Biological Anthropology, National Research Centre, Cairo, Egypt
| | - Eman Youness
- Department of Biological Anthropology, National Research Centre, Cairo, Egypt
| | - Khaled Hamed
- Clinical Genetics Department, Center of Scientific Excellence, National Research Centre, Cairo, Egypt
| | - Azzah A. Khedr
- Human Genetics and Genome Research Division, Human Cytogenetics Department, National Research Centre, Cairo, Egypt
| | - Phoebe M. Abd El-Massieh
- Human Genetics and Genome Research Division, Oro-dental Genetics Department, National Research Centre, Cairo, Egypt
| | - Sara M. Abdo
- Biochemistry Division, Chemistry Department, Faculty of Science, Helwan University, Cairo, Egypt
| | - Hala T. El-Bassyouni
- Clinical Genetics Department, Center of Scientific Excellence, National Research Centre, Cairo, Egypt
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Hashimoto M, Tanabe Y, Hossain S, Matsuzaki K, Ohno M, Kato S, Katakura M, Shido O. Intake of Alpha-Linolenic Acid-Rich Perilla frutescens Leaf Powder Decreases Home Blood Pressure and Serum Oxidized Low-Density Lipoprotein in Japanese Adults. Molecules 2020; 25:molecules25092099. [PMID: 32365849 PMCID: PMC7248687 DOI: 10.3390/molecules25092099] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2020] [Revised: 04/28/2020] [Accepted: 04/29/2020] [Indexed: 12/11/2022] Open
Abstract
Oxidized low-density lipoprotein (Ox-LDL) is known to be highly atherogenic. Thus, decreasing the blood levels of Ox-LDL through dietary means is an important approach to reduce cardiovascular events in high-risk individuals. In this randomized placebo-controlled human interventional trial, we aimed to evaluate whether Perilla frutescens leaf powder (PLP) ameliorates Ox-LDL and home blood pressure, along with its biological antioxidant potential. Healthy Japanese volunteers aged 30-60 years (n = 60) were randomized to PLP and placebo groups. The PLP group consumed PLP dried using a microwave under reduced pressure, and the placebo group consumed pectin fiber daily for 6 months. Home blood pressure, serum biochemical parameters, and fatty acid profiles of erythrocyte plasma membranes were analyzed. Plasma Ox-LDL levels significantly decreased in the PLP group but not in the placebo group. Mean changes in the biological antioxidant potential and alpha-linolenic acid levels in the erythrocyte plasma membrane were significantly increased in the PLP group than in the placebo group. In subjects with prehypertension (systolic blood pressure [SBP] ³ 120 mmHg), the mean reduction in morning or nocturnal SBP was significantly greater in the PLP group than in the placebo group. Thus, PLP intake may be an effective intervention to prevent cardiovascular diseases.
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Affiliation(s)
- Michio Hashimoto
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo 693-8501, Shimane, Japan; (Y.T.); (K.M.); (M.K.); (O.S.)
- Correspondence: ; Tel.: +81-853-20-2730
| | - Yoko Tanabe
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo 693-8501, Shimane, Japan; (Y.T.); (K.M.); (M.K.); (O.S.)
| | - Shahdat Hossain
- Department of Biochemistry and Molecular Biology, Jahangirnagar University, Savar, Dhaka 1342, Bangladesh;
| | - Kentaro Matsuzaki
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo 693-8501, Shimane, Japan; (Y.T.); (K.M.); (M.K.); (O.S.)
| | - Miho Ohno
- Kato Hospital, Jinjukai Healthcare Corporation, Kawamoto, Shimane 696-0001, Japan; (M.O.); (S.K.)
| | - Setsushi Kato
- Kato Hospital, Jinjukai Healthcare Corporation, Kawamoto, Shimane 696-0001, Japan; (M.O.); (S.K.)
| | - Masanori Katakura
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo 693-8501, Shimane, Japan; (Y.T.); (K.M.); (M.K.); (O.S.)
| | - Osamu Shido
- Department of Environmental Physiology, Faculty of Medicine, Shimane University, Izumo 693-8501, Shimane, Japan; (Y.T.); (K.M.); (M.K.); (O.S.)
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Oxidized LDL Modify the Human Adipocyte Phenotype to an Insulin Resistant, Proinflamatory and Proapoptotic Profile. Biomolecules 2020; 10:biom10040534. [PMID: 32244787 PMCID: PMC7226150 DOI: 10.3390/biom10040534] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2020] [Revised: 03/19/2020] [Accepted: 03/25/2020] [Indexed: 12/17/2022] Open
Abstract
Little information exists in humans on the regulation that oxidized low-density lipoprotein (oxLDL) exerts on adipocyte metabolism, which is associated with obesity and type 2 diabetes. The aim was to analyze the oxLDL effects on adipocytokine secretion and scavenger receptors (SRs) and cell death markers in human visceral adipocytes. Human differentiated adipocytes from visceral adipose tissue from non-obese and morbidly obese subjects were incubated with increasing oxLDL concentrations. mRNA expression of SRs, markers of apoptosis and autophagy, secretion of adipocytokines, and glucose uptake were analyzed. In non-obese and in morbidly obese subjects, oxLDL produced a decrease in insulin-induced glucose uptake, a significant dose-dependent increase in tumor necrosis factor-α (TNF-α), IL-6, and adiponectin secretion, and a decrease in leptin secretion. OxLDL produced a significant increase of Lox-1 and a decrease in Cxcl16 and Cl-p1 expression. The expression of Bnip3 (marker of apoptosis, necrosis and autophagy) was significantly increased and Bcl2 (antiapoptotic marker) was decreased. OxLDL could sensitize adipocytes to a lower insulin-induced glucose uptake, a more proinflammatory phenotype, and could modify the gene expression involved in apoptosis, autophagy, necrosis, and mitophagy. OxLDL can upregulate Lox-1, and this could lead to a possible amplification of proinflammatory and proapoptotic effects of oxLDL.
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Al Shawaf E, Al-Ozairi E, Al-Asfar F, Mohammad A, Al-Beloushi S, Devarajan S, Al-Mulla F, Abubaker J, Arefanian H. Atherogenic Index of Plasma (AIP) a Tool to Assess Changes in Cardiovascular Disease Risk Post Laparoscopic Sleeve Gastrectomy. J Diabetes Res 2020; 2020:2091341. [PMID: 32832558 PMCID: PMC7422485 DOI: 10.1155/2020/2091341] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/21/2020] [Revised: 07/08/2020] [Accepted: 07/13/2020] [Indexed: 01/08/2023] Open
Abstract
Predictive indices like the atherogenic index of plasma (AIP) have been developed to estimate the risk of cardiovascular disease (CVD). Metabolic surgery is the most effective treatment for a rapid improvement of morbid obesity and its comorbidities such as type 2 diabetes (T2D) and CVD. A decreased reoccurrence of CVD after metabolic surgery has been reported by several studies. However, studies utilizing predictive indices for CVD risk in CVD-free morbid-obese patients who undertook laparoscopic sleeve gastrectomy (LSG) are lacking. Here, we use AIP as a tool to evaluate the improvement in CVD risk post-LSG in morbid-obese people who had no history of CVD. Method. We compared baseline, 6- and 12-month post-LSG score of AIP, vascular age, circulating biochemical markers related to CVD in two groups of BMI and age-matched morbid-obese participants with and without T2D. Results. At baseline, people with T2D had significantly higher AIP both, with morbid obesity (0.23 ± 0.06, p < 0.001) and normal weight (0.022 ± 0.05, p < 0.001) compared to their BMI-matched without T2D group. People with morbid obesity had low AIP (-0.083 ± 0.06). Vascular age was significantly higher in people with morbid obesity and T2D (65.8 ± 3.7year, p < 0.0001) compared to morbid obesity (37.9 ± 2.6 year). After one year, AIP was significantly reduced compared to baseline score in people with morbid obesity with/without T2D, respectively (-0.135 ± 0.07, p = 0.003; and -0.36 ± 0.04, p = 0.0002). Conclusion. Our data illuminates AIP as a reliable predictive index for CVD risk in morbid-obese people who had no history of CVD. Moreover, AIP accurately distinguishes between morbid obesity with T2D and morbid obesity and showed a rapid and significant reduction in CVD risk after LSG in people who had no history of CVD. This is a ClinicalTrials.gov registered trial (Reference NCT03038373).
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Affiliation(s)
- Eman Al Shawaf
- Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait
| | - Ebaa Al-Ozairi
- Medical Division, Clinical Research Unit, Dasman Diabetes institute, Kuwait
| | - Fahad Al-Asfar
- Departement of Surgery, Faculty of Medicine, Kuwait University, Kuwait
| | - Anwar Mohammad
- Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait
| | - Shaima Al-Beloushi
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Kuwait
| | | | - Fahd Al-Mulla
- Research Division, Dasman Diabetes Institute, Kuwait
| | - Jehad Abubaker
- Department of Biochemistry and Molecular Biology, Dasman Diabetes Institute, Kuwait
| | - Hossein Arefanian
- Department of Immunology and Microbiology, Dasman Diabetes Institute, Kuwait
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Holvoet P, Klocke B, Vanhaverbeke M, Menten R, Sinnaeve P, Raitoharju E, Lehtimäki T, Oksala N, Zinser C, Janssens S, Sipido K, Lyytikainen LP, Cagnin S. RNA-sequencing reveals that STRN, ZNF484 and WNK1 add to the value of mitochondrial MT-COI and COX10 as markers of unstable coronary artery disease. PLoS One 2019; 14:e0225621. [PMID: 31821324 PMCID: PMC6903720 DOI: 10.1371/journal.pone.0225621] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2019] [Accepted: 11/09/2019] [Indexed: 12/23/2022] Open
Abstract
Markers in monocytes, precursors of macrophages, which are related to CAD, are largely unknown. Therefore, we aimed to identify genes in monocytes predictive of a new ischemic event in patients with CAD and/or discriminate between stable CAD and acute coronary syndrome. We included 66 patients with stable CAD, of which 24 developed a new ischemic event, and 19 patients with ACS. Circulating CD14+ monocytes were isolated with magnetic beads. RNA sequencing analysis in monocytes of patients with (n = 13) versus without (n = 11) ischemic event at follow-up and in patients with ACS (n = 12) was validated with qPCR (n = 85). MT-COI, STRN and COX10 predicted new ischemic events in CAD patients (power for separation at 1% error rate of 0.97, 0.90 and 0.77 respectively). Low MT-COI and high STRN were also related to shorter time between blood sampling and event. COX10 and ZNF484 together with MT-COI, STRN and WNK1 separated ACS completely from stable CAD patients. RNA expressions in monocytes of MT-COI, COX10, STRN, WNK1 and ZNF484 were independent of cholesterol lowering and antiplatelet treatment. They were independent of troponin T, a marker of myocardial injury. But, COX10 and ZNF484 in human plaques correlated to plaque markers of M1 macrophage polarization, reflecting vascular injury. Expression of MT-COI, COX10, STRN and WNK1, but not that of ZNF484, PBMCs paired with that in monocytes. The prospective study of relation of MT-COI, COX10, STRN, WNK1 and ZNF484 with unstable CAD is warranted.
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Affiliation(s)
- Paul Holvoet
- Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
- * E-mail:
| | | | | | - Roxane Menten
- Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
| | - Peter Sinnaeve
- Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium
| | - Emma Raitoharju
- Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
- Finnish Cardiovascular Research Centre, Faculty of Medicine and Life Sciences University of Tampere, Tampere, Finland
| | - Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
- Finnish Cardiovascular Research Centre, Faculty of Medicine and Life Sciences University of Tampere, Tampere, Finland
| | - Niku Oksala
- Division of Vascular Surgery, Department of Surgery, Tampere University Hospital, Tampere, Finland
| | | | - Stefan Janssens
- Department of Clinical Cardiology, UZ Leuven, Leuven, Belgium
| | - Karin Sipido
- Department of Cardiovascular Sciences, KU Leuven, Leuven, Belgium
| | - Leo-Pekka Lyytikainen
- Department of Clinical Chemistry, Fimlab Laboratories, Tampere, Finland
- Finnish Cardiovascular Research Centre, Faculty of Medicine and Life Sciences University of Tampere, Tampere, Finland
| | - Stefano Cagnin
- Department of Biology, CRIBI Biotechnology Centre, Padova, Italy
- CIR-Myo Myology Centre, University of Padova, Padova, Italy
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Dimova R, Chakarova N, Grozeva G, Kirilov G, Tankova T. The relationship between glucose variability and insulin sensitivity and oxidative stress in subjects with prediabetes. Diabetes Res Clin Pract 2019; 158:107911. [PMID: 31707004 DOI: 10.1016/j.diabres.2019.107911] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2019] [Revised: 10/13/2019] [Accepted: 10/28/2019] [Indexed: 12/21/2022]
Abstract
AIM The present study assessed the relationship between glucose variability (GV) and insulin levels, insulin resistance and oxidative stress at early stages of glucose intolerance. MATERIAL AND METHODS A total of 50 subjects - 12 males and 38 females, mean age 55.6 ± 9.7 years, mean BMI 28.4 ± 6.4 kg/m2, divided into 2 groups according to glucose tolerance: 32 with prediabetes and 18 with normal glucose tolerance were included. Glucose tolerance was assessed by OGTT according to WHO 2006 criteria. Plasma glucose and serum insulin were measured at fasting, 120-minute and 180-minute during the test; and oxLDL and 3-Nitrotyrosine - at fasting and 120-minute. HOMA-IR and OGIS indexes were calculated. HbA1c and lipid levels was assessed. Continuous glucose monitoring was performed with a blind sensor (FreeStyle Libre Pro) for a mean period of 13.6 ± 2.3 days. RESULTS Our results demonstrate significantly increased insulin resistance in subjects with prediabetes, whereas there is no difference in oxidative stress markers between the two groups. OxLDL and 3-NT correlate positively with insulin levels and HOMA-IR and negatively with OGIS in both groups. There is a positive association between oxidative stress markers and 120-minute glucose in the prediabetes group. Insulin levels and HOMA-IR are positively related to plasma glucose and reciprocally to CV and M-Value in prediabetes, since the latter association is with borderline significance after adjustment for hypertension and smoking. CONCLUSIONS Our results demonstrate a significant correlation between oxidative stress and insulin resistance at early stages of glucose intolerance. Both chronic hyperglycemia and GV seem to be related to insulin levels and insulin resistance, and just postload glycaemia to oxidative stress in prediabetes.
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Affiliation(s)
- Rumyana Dimova
- Department of Endocrinology, Medical University - Sofia, Bulgaria.
| | - Nevena Chakarova
- Department of Endocrinology, Medical University - Sofia, Bulgaria
| | - Greta Grozeva
- Department of Endocrinology, Medical University - Sofia, Bulgaria
| | - Georgi Kirilov
- Department of Endocrinology, Medical University - Sofia, Bulgaria
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Prestroke statins use reduces oxidized low density lipoprotein levels and improves clinical outcomes in patients with atrial fibrillation related acute ischemic stroke. BMC Neurol 2019; 19:240. [PMID: 31627722 PMCID: PMC6800490 DOI: 10.1186/s12883-019-1463-7] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2019] [Accepted: 09/11/2019] [Indexed: 01/09/2023] Open
Abstract
Background Atrial fibrillation (AF) is a common cause of cerebral infarction, which could lead to endothelial dysfunction, increased reactive oxygen species (ROS) and oxidized low density lipoprotein (Ox-LDL).AF is associated with higher mortality and more severe neurologic disability. Statins may exert neuroprotective effects that are independent of LDL-C lowering. The purpose of our study was to investigate whether prestroke statins use could reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related acute ischemic stroke (AIS). Methods This was a multicenter prospective study that involved four medical centers, 242 AIS patients with AF were identified, who underwent a comprehensive clinical investigation and a 72 h-Holter electrocardiogram monitoring. All patients were divided into two groups: prestroke statins use and no prestroke statins use groups, who were followed up for 3 months. Plasma Ox-LDL levels were measured using enzyme-linked immunosorbent assay (ELISA) on admission and at 3 months. The outcome was death, major disability (modified Rankin Scale score ≥ 3), and composite outcome (death/major disability) at 3 months after AIS. Results One hundred thirty-six patients were in no prestroke statins use group, and 106 in prestroke statins use group. Plasma Ox-LDL levels were significantly lower in prestroke statins use than in no prestroke statins use on admission and at 3 months (P < 0.001). Plasma Ox-LDL levels on admission were associated with 3-month mortality [adjusted odds ratio (OR), 1.05; 95% confidence interval (CI), 0.99–1.12; P = 0.047]. In fully adjusted models, prestroke statins use was associated with reduced 3-month mortality [adjusted OR, 0.38; 95% CI, 0.16–0.91; P = 0.031)], major disability (adjusted OR, 0.38; 95% CI, 0.15–0.99; P = 0.047), and composite outcome (adjusted OR, 0.31; 95% CI, 0.17–0.74; P = 0.009). Conclusions Prestroke statins use can reduce plasma Ox-LDL levels and improve clinical outcomes in patients with AF-related AIS.
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Yang XL, Cui ZZ, Zhang H, Wei XT, Feng GJ, Liu L, Liu YZ, Pei YF, Zhang L. Causal link between lipid profile and bone mineral density: A Mendelian randomization study. Bone 2019; 127:37-43. [PMID: 31158506 DOI: 10.1016/j.bone.2019.05.037] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Revised: 05/14/2019] [Accepted: 05/29/2019] [Indexed: 01/14/2023]
Abstract
The level of serum lipids is associated with bone mineral density (BMD), an important skeletal trait. Yet the causality has not been determined. Here we performed a Mendelian randomization (MR) analysis to test potential causal links between BMD and lipid profile, i.e., low-density lipoprotein cholesterol (LDC-c), total cholesterol (TC), triglyceride (TG) and high-density lipoprotein cholesterol (HDL-c). We observed causal effect of LDL-c, TC and TG to BMD, and reversely the effect of BMD to HDL-c. We further explored the effect of body mass index (BMI) in these causalities and found that the effect of LDL-c, TC and TG to BMD is independent of BMI. Our findings provided useful information in the clinical relevance of blood lipids on BMD variation and osteoporosis risk.
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Affiliation(s)
- Xiao-Lin Yang
- Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Jiangsu, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, PR China.
| | - Zhi-Zhen Cui
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, PR China; Department of Child Health, School of Public Health, Medical College of Soochow University, Jiangsu, PR China
| | - Hong Zhang
- Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Jiangsu, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, PR China
| | - Xin-Tong Wei
- Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Jiangsu, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, PR China
| | - Gui-Juan Feng
- Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Jiangsu, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, PR China
| | - Lu Liu
- Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Jiangsu, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, PR China
| | - Yao-Zhong Liu
- Department of Global Biostatistics and Data Science, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA, USA.
| | - Yu-Fang Pei
- Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, PR China; Department of Epidemiology and Health Statistics, School of Public Health, Medical College, Soochow University, Jiangsu, PR China.
| | - Lei Zhang
- Center for Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Jiangsu, PR China; Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, PR China.
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Awadallah S, Hasan H, Attlee A, Raigangar V, Unnikannan H, Madkour M, Abraham MS, Rashid LM. Waist circumference is a major determinant of oxidative stress in subjects with and without metabolic syndrome. Diabetes Metab Syndr 2019; 13:2541-2547. [PMID: 31405674 DOI: 10.1016/j.dsx.2019.07.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2019] [Accepted: 07/08/2019] [Indexed: 12/30/2022]
Abstract
AIM Oxidative stress (OS) plays a major role in pathogenic mechanisms associated with metabolic syndrome (Mets) yet the main component of Mets contributing most to OS is not well elucidated. Hence, the aim of this study was to investigate the oxidative-antioxidative status in Mets subjects and to determine the main predicting component of OS. METHODS Anthropometric measures, fasting blood glucose, lipid profile, antioxidant enzymes [catalase, superoxide dismutase (SOD) and glutathione peroxidase (GPx)], reduced glutathione (GSH), malondialdehyde (MDA) and protein carbonyl were assessed in 172 adult UAE residents. International Diabetes Federation criteria were used for Mets diagnosis. Mets Scores (0-5) were calculated and assigned per subject based on number of components. RESULTS Of all participants, 22.1% had Mets and 49.4% had large waist circumference (WC). Significant lower levels of catalase, SOD, GPx and GSH, and higher levels of MDA and protein carbonyl were observed in subjects with Mets. In addition, catalase, SOD, GPx, and GSH correlated negatively, while MDA and protein carbonyl correlated positively with almost all Mets components. Similar trend of correlations was noticed with Mets Scores. When adjusted for age and gender, linear regression analysis revealed that subjects with large WC demonstrated significantly lower levels of antioxidative enzymes and GSH, and higher levels of MDA and protein carbonyl. Consequently, WC emerged as the best predictor of OS. CONCLUSIONS The degree of OS is dependent on the Mets Scores, and WC contributes independently to increased OS among adults in UAE.
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Affiliation(s)
- Samir Awadallah
- College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates.
| | - Hayder Hasan
- College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Amita Attlee
- Nutrition and Health Department, College of Food and Agriculture, United Arab Emirates University, Al Ain, United Arab Emirates
| | - Veena Raigangar
- College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Hema Unnikannan
- Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Mohamed Madkour
- College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates; Research Institute for Medical and Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Mini Sara Abraham
- College of Health Sciences, University of Sharjah, Sharjah, United Arab Emirates
| | - Latifa M Rashid
- Head of Nutrition Section, Ministry of Health and Prevention, United Arab Emirates
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Itabe H, Kato R, Sawada N, Obama T, Yamamoto M. The Significance of Oxidized Low-Density Lipoprotein in Body Fluids as a Marker Related to Diseased Conditions. Curr Med Chem 2019. [PMID: 29521196 DOI: 10.2174/0929867325666180307114855] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Oxidatively modified low-density lipoprotein (oxLDL) is known to be involved in various diseases, including cardiovascular diseases. The presence of oxLDL in the human circulatory system and in atherosclerotic lesions has been demonstrated using monoclonal antibodies. Studies have shown the significance of circulating oxLDL in various systemic diseases, including acute myocardial infarction and diabetic mellitus. Several different enzyme-linked immunosorbent assay (ELISA) procedures to measure oxLDL were utilized. Evidence has been accumulating that reveals changes in oxLDL levels under certain pathological conditions. Since oxLDL concentration tends to correlate with low-density lipoprotein (LDL)-cholesterol, the ratio of ox-LDL and LDL rather than oxLDL concentration alone has also been focused. In addition to circulating plasma, LDL and oxLDL are found in gingival crevicular fluid (GCF), where the ratio of oxLDL to LDL in GCF is much higher than in plasma. LDL and oxLDL levels in GCF show an increase in diabetic patients and periodontal patients, suggesting that GCF might be useful in examining systemic conditions. GCF oxLDL increased when the teeth were affected by periodontitis. It is likely that oxLDL levels in plasma and GCF could reflect oxidative stress and transfer efficacy in the circulatory system.
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Affiliation(s)
- Hiroyuki Itabe
- Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo, Japan
| | - Rina Kato
- Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo, Japan
| | - Naoko Sawada
- Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo, Japan
| | - Takashi Obama
- Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, Tokyo, Japan
| | - Matsuo Yamamoto
- Department of Periodontology, Showa University School of Dentistry, Tokyo, Japan
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40
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Pokimica B, García-Conesa MT, Zec M, Debeljak-Martačić J, Ranković S, Vidović N, Petrović-Oggiano G, Konić-Ristić A, Glibetić M. Chokeberry Juice Containing Polyphenols Does Not Affect Cholesterol or Blood Pressure but Modifies the Composition of Plasma Phospholipids Fatty Acids in Individuals at Cardiovascular Risk. Nutrients 2019; 11:E850. [PMID: 30991718 PMCID: PMC6520894 DOI: 10.3390/nu11040850] [Citation(s) in RCA: 32] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2019] [Revised: 04/09/2019] [Accepted: 04/10/2019] [Indexed: 12/17/2022] Open
Abstract
Chokeberry polyphenols have been suggested to reduce cholesterol and blood pressure and thus protect against cardiovascular diseases (CVD), but the evidence in humans is limited and inconsistent. This randomized double-blinded three-parallel groups trial investigated the changes in various anthropometric and clinical biomarkers, and in plasma phospholipids fatty acids (PPFA) in volunteers at cardiovascular risk after a four-week intervention with 100 mL/day of (1) chokeberry juice with a high-dose of polyphenols (1177.11 mg gallic acid equivalents, GAE); (2) chokeberry juice with a low-dose of polyphenols (294.28 mg GAE) and; (3) a nutritionally matched polyphenol-free placebo drink. Our results indicate that the intake of chokeberry juice containing either the low or the high dose of polyphenols cannot be linked with a reduction in total- and low-density lipoprotein (LDL)cholesterol or in systolic (SBP) and diastolic (DBP) blood pressure in comparison with the consumption of the placebo drink. However, we found evidence of moderate changes in the PPFA, i.e., increased saturated fatty acids (SFA), mostly palmitic acid, and reduced n-6 polyunsaturated fatty acids (PUFA), principally linoleic acid (LA) with the intake of chokeberry against the placebo. These effects may be associated with the polyphenols but we could not differentiate a clear dose-response effect. Further research is still needed to elucidate the contribution of the polyphenolic fraction to the potential cardiovascular effects of the chokeberry and to build up the evidence of its potential benefit via the modulation of PPFA composition.
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Affiliation(s)
- Biljana Pokimica
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia.
| | - María-Teresa García-Conesa
- Research Group on Quality, Safety and Bioactivity of Plant Foods, Campus de Espinardo, Centro de Edafología y Biología Aplicada del Segura-Consejo Superior de Investigaciones Científicas (CEBAS-CSIC), P.O. Box 164, 30100 Murcia, Spain.
| | - Manja Zec
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia.
| | - Jasmina Debeljak-Martačić
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia.
| | - Slavica Ranković
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia.
| | - Nevena Vidović
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia.
| | - Gordana Petrović-Oggiano
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia.
| | - Aleksandra Konić-Ristić
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia.
| | - Maria Glibetić
- Center of Research Excellence in Nutrition and Metabolism, Institute for Medical Research, University of Belgrade, 11000 Belgrade, Serbia.
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41
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Ho CM, Ho SL, Jeng YM, Lai YS, Chen YH, Lu SC, Chen HL, Chang PY, Hu RH, Lee PH. Accumulation of free cholesterol and oxidized low-density lipoprotein is associated with portal inflammation and fibrosis in nonalcoholic fatty liver disease. JOURNAL OF INFLAMMATION-LONDON 2019; 16:7. [PMID: 30983887 PMCID: PMC6444889 DOI: 10.1186/s12950-019-0211-5] [Citation(s) in RCA: 40] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/16/2018] [Accepted: 03/12/2019] [Indexed: 12/13/2022]
Abstract
Background Macrophages engulf oxidized-LDL (oxLDL) leading to accumulation of cellular cholesterol and formation of foam cells, which is a hallmark of atherosclerosis. Moreover, recent studies showed that accumulation of free cholesterol in macrophages leading to activation of NLRP3 inflammasome and production of interleukin-1β (IL-1β) has been linked to atherosclerosis-associated inflammation. However, it is not clear if cholesterol accumulation is associated with hepatic inflammation and fibrosis in the liver. In this study, we investigated the association of free cholesterol and oxLDL accumulation in portal vein with the inflammation, atherosclerosis, and fibrosis in human nonalcoholic fatty liver disease (NAFLD). Methods Serial sections derived from surgical specimens of NAFLD were stained with filipin and antibodies against IL-1β, CD68, α-smooth muscle actin (α-SMA), oxLDL and lectin-like oxLDL receptor-1 (LOX-1). Results We show that free cholesterol was colocalized with oxLDL in the wall of portal vein, and which was associated with lumen narrowing, plaque formation, endothelium deformation, and portal venous inflammation. The inflammation was evidenced by the colocalization of Kupffer cells and IL-1β and the expression of LOX-1. Notably, ruptured plaque was closely associated with portal venous inflammation. Moreover, free cholesterol and oxLDL accumulation in periportal and sinusoidal fibrosis, which was associated with regional stellate cell activation and chicken-wire fibrosis. Conclusion These findings reveal a direct association between cholesterol accumulation, portal venous inflammation and fibrosis in NAFLD. Electronic supplementary material The online version of this article (10.1186/s12950-019-0211-5) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Cheng-Maw Ho
- 1Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.,2Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan
| | - Shu-Li Ho
- 1Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.,2Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan.,8Department of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan
| | - Yung-Ming Jeng
- 3Department of Pathology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Yu-Sheng Lai
- 4Department of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, 1, Jen Ai Rd, Sec 1, Taipei, 100 Taiwan
| | - Ya-Hui Chen
- 2Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan.,5Department of Pediatrics, National Taiwan University Children Hospital, Taipei, Taiwan
| | - Shao-Chun Lu
- 4Department of Biochemistry and Molecular Biology, National Taiwan University College of Medicine, 1, Jen Ai Rd, Sec 1, Taipei, 100 Taiwan
| | - Hui-Ling Chen
- 2Hepatitis Research Center, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, 100 Taiwan
| | - Po-Yuan Chang
- 6Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Rey-Heng Hu
- 1Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan
| | - Po-Huang Lee
- 1Department of Surgery, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan.,7Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
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Haghighatdoost F, Hariri M. Does alpha-lipoic acid affect lipid profile? A meta-analysis and systematic review on randomized controlled trials. Eur J Pharmacol 2019; 847:1-10. [DOI: 10.1016/j.ejphar.2019.01.001] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Revised: 12/22/2018] [Accepted: 01/07/2019] [Indexed: 12/29/2022]
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DUSP1 Is a Potential Marker of Chronic Inflammation in Arabs with Cardiovascular Diseases. DISEASE MARKERS 2019; 2018:9529621. [PMID: 30647800 PMCID: PMC6311887 DOI: 10.1155/2018/9529621] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/01/2018] [Accepted: 12/03/2018] [Indexed: 11/17/2022]
Abstract
Background Cardiovascular disease (CVD) risks persist in patients despite the use of conventional treatments. This might be due to chronic inflammation as reflected in epidemiological studies associating circulating low-grade inflammatory markers with CVD recurrent events. Here, we explored this potential link by assessing plasma dual-specificity phosphatase 1 (DUSP1) levels and comparing them to high-sensitivity CRP (hsCRP) and oxidized low-density lipoprotein (oxLDL) levels and their associations to conventional CVD risk factors in confirmed CVD patients. Methods Human adults with reported CVD (n = 207) and controls (n = 70) living in Kuwait were used in this study. Anthropometric and classical biochemical parameters were determined. Plasma levels of DUSP1, oxLDL, and hsCRP were measured using human enzyme-linked immunosorbent assay kits. Results DUSP1 and hsCRP plasma levels and their least square means were higher in CVD cases, while oxLDL plasma levels were lower (p < 0.05). Multivariate logistic regression analysis showed that DUSP1 and hsCRP are independently associated with CVD in the studied population, as reflected by 2-fold and 1.5-fold increased risks with increased levels of DUSP1 and hsCRP, respectively. In our study, DUSP1 levels were found to be associated with CVD despite statin treatment and diabetes status (p < 0.05), whereas hsCRP mainly correlated with obesity markers. Conclusions Circulating DUSP1 might be a predictor of chronic subclinical inflammation and residual risk in CVD patients, whereas our data suggest that the association between hsCRP and CVD is largely accounted for adiposity risk factors.
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Onaolapo AY, Onaolapo OJ. Nutraceuticals and Diet-based Phytochemicals in Type 2 Diabetes Mellitus: From Whole Food to Components with Defined Roles and Mechanisms. Curr Diabetes Rev 2019; 16:12-25. [PMID: 30378500 DOI: 10.2174/1573399814666181031103930] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2018] [Revised: 10/19/2018] [Accepted: 10/23/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND Over the past decades, the development and use of an array of prescription medications have considerably improved the clinical management of type 2 diabetes mellitus and the quality of life of patients. However, as our knowledge of the associated risk factors and approaches to its management increases, the increasing roles of diet and the composition of the diet in the etiology and successful management of diabetes mellitus are being illuminated. Presently, a lot of attention is being given to nutraceuticals and certain phytochemicals that are integral parts of the human diet. It is believed that a clearer understanding of their roles may be crucial to 'non-invasive' or minimallyintrusive management, with regards to daily living of patients. In this review, an overview of nutraceutical components and phytochemicals that may be of benefit, or had been known to be beneficial in diabetes mellitus is given. Also, how the roles of such dietary components are evolving in the management of this disorder is highlighted. Lastly, the obstacles that need to be overcome before nutraceuticals can be considered as options for the clinical management of diabetes mellitus areconsidered. CONCLUSION Despite studies that demonstrate their efficacy, no nutraceutical or food-derived compound has been formally adopted as a direct replacement for any class of antidiabetic drugs.
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Affiliation(s)
- Adejoke Yetunde Onaolapo
- Behavioural Neuroscience/Neurobiology Unit, Department of Anatomy, Ladoke Akintola University of Technology, Ogbomosho, Oyo State, Nigeria
| | - Olakunle James Onaolapo
- Department of Pharmacology, Behavioural Neuroscience/Neuropharmacology Unit, Ladoke Akintola University of Technology, Osogbo, Osun State, Nigeria
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45
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Funderburk L, Peterson M, Beretich K, Shah N, Grandjean PW. Prevalence of metabolic disease and correlation to body composition and cardiovascular fitness in adults undergoing fitness assessments. PLoS One 2018; 13:e0209514. [PMID: 30576347 PMCID: PMC6303013 DOI: 10.1371/journal.pone.0209514] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/20/2018] [Accepted: 12/06/2018] [Indexed: 12/29/2022] Open
Abstract
The purpose of this descriptive study was to assess the prevalence of metabolic syndrome (MetS), prediabetes and type 2 diabetes (T2DM) in participants who voluntarily participated in a fitness assessment, and to examine associations with routine nutrition intake and overall body composition. One hundred and six participants were recruited. Anthropometric measurements were taken with blood analyses completed for fasting glucose, glycosylated hemoglobin (HbA1c) and lipid panel. A 24-hour diet recall and a dietary screening survey was used to assess nutrient intake, in a sub-set of 36 participants. Statistical analyses utilized partial Spearmans' rank correlations, risk ratios, and Kendall's Tau correlations, with significance level at p < 0.05. Twenty five percent of this sample had ≥ three risk factors for MetS, with elevated fasting glucose and blood pressure being the most prevalent. Twenty percent of the participants had HbA1c levels elevated at the prediabetes range, with no previous diagnosis. Four percent of participants had HbA1c levels elevated at the T2DM range. Two nutrients of interest were correlated to BMI status. Percent kcal from carbohydrate (τ -0.207, p<0.05) had a negative correlation with BMI status and percent kcal from fat intake had a positive correlation (τ 0.217, p<0.05). Findings from this small sample of adults indicate the need for routine assessment of: clustering of MetS risk factors, risk of prediabetes and T2DM and treatment of same. Many participants would benefit from increasing their participation in physical activity, weight loss in regard to overall health improvement, and education to improve diet quality.
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Affiliation(s)
- LesLee Funderburk
- Robbins College of Health and Human Sciences, Baylor University, Waco, Texas, United States of America
- * E-mail:
| | - Matthew Peterson
- Robbins College of Health and Human Sciences, Baylor University, Waco, Texas, United States of America
| | - Kaitlan Beretich
- Robbins College of Health and Human Sciences, Baylor University, Waco, Texas, United States of America
| | - Nish Shah
- Orthopedics and Sports Medicine, Houston Methodist, Sugarland, Texas, United States of America
| | - Peter W. Grandjean
- Robbins College of Health and Human Sciences, Baylor University, Waco, Texas, United States of America
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46
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Brede S, Lehnert H. [Nutrition in type 2 diabetes mellitus]. Internist (Berl) 2018; 60:49-58. [PMID: 30560369 DOI: 10.1007/s00108-018-0531-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
The increasing incidence of metabolic diseases, such as type 2 diabetes mellitus, poses a major problem for the healthcare system. Healthy food habits represent an important therapeutic measure to prevent health sequelae, such as cardiovascular diseases. According to recent data these are less due to individual dietary components and more to the composition of nutrition. A positive effect on glucose and fat metabolism in type 2 diabetes has been confirmed for various forms of nutrition. In addition to the type of nutrition, the so-called glycemic index of foodstuffs is also decisive for blood glucose control. Additionally, beneficial effects for particular foodstuffs, such as coffee, could be determined in patients with diabetes.
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Affiliation(s)
- S Brede
- Medizinische Klinik 1, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland.
| | - H Lehnert
- Medizinische Klinik 1, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Ratzeburger Allee 160, 23538, Lübeck, Deutschland.,Deutsches Zentrum für Diabetesforschung e. V. (DZD), Lübeck, Deutschland
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Spratlen MJ, Grau-Perez M, Umans JG, Yracheta J, Best LG, Francesconi K, Goessler W, Balakrishnan P, Cole SA, Gamble MV, Howard BV, Navas-Acien A. Arsenic, one carbon metabolism and diabetes-related outcomes in the Strong Heart Family Study. ENVIRONMENT INTERNATIONAL 2018; 121:728-740. [PMID: 30321848 PMCID: PMC6221918 DOI: 10.1016/j.envint.2018.09.048] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 09/25/2018] [Accepted: 09/26/2018] [Indexed: 05/02/2023]
Abstract
BACKGROUND Inorganic arsenic exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. A more efficient arsenic metabolism profile (lower MMA%, higher DMA%) has been associated with reduced risk for arsenic-related health outcomes; however, this profile has also been associated with increased risk for diabetes-related outcomes. The mechanism behind these contrasting associations is equivocal; we hypothesized one carbon metabolism (OCM) may play a role. METHODS We evaluated the association between OCM-related variables (nutrient intake and genetic variants) and both arsenic metabolism biomarkers (iAs%, MMA% and DMA%) and diabetes-related outcomes (metabolic syndrome, diabetes, HOMA2-IR and waist circumference) in 935 participants free of prevalent diabetes and metabolic syndrome from the Strong Heart Family Study, a family-based prospective cohort comprised of American Indian tribal members aged 14+ years. RESULTS Of the 935 participants free of both diabetes and metabolic syndrome at baseline, 279 (29.8%) developed metabolic syndrome over a median of 5.3 years of follow-up and of the 1458 participants free of diabetes at baseline, 167 (11.3%) developed diabetes over follow-up. OCM nutrients were not associated with arsenic metabolism, however, higher vitamin B6 was associated with diabetes-related outcomes (higher HOMA2-IR and increased risk for diabetes and metabolic syndrome). A polymorphism in an OCM-related gene, methionine synthase (MTR), was associated with both higher MMA% (β = 2.57, 95% CI: 0.22, 4.92) and lower HOMA2-IR (GMR = 0.79, 95% CI = 0.66, 0.93 per 5 years of follow-up). Adjustment for OCM variables did not affect previously reported associations between arsenic metabolism and diabetes-related outcomes; however, the association between the MTR variant and diabetes-related outcomes were attenuated after adjustment for arsenic metabolism. CONCLUSIONS Our findings suggest MMA% may be a partial mediator in the association between OCM and diabetes-related outcomes. Additional mediation analyses with longer follow-up period are needed to confirm this finding. Further research is needed to determine whether excess B vitamin intake is associated with increased risk for diabetes-related outcomes.
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Affiliation(s)
- Miranda J Spratlen
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America; Department of Environmental Health & Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America.
| | - Maria Grau-Perez
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America; Fundación Investigación Clínico de Valencia-INCLIVA, Area of Cardiometabolic and Renal Risk, Valencia, Spain; Department of Statistics and Operational Research, University of Valencia, Valencia, Spain
| | - Jason G Umans
- MedStar Health Research Institute, Hyattsville, MD, United States of America; Department of Medicine, Georgetown University School of Medicine, Washington, DC, United States of America
| | - Joseph Yracheta
- Missouri Breaks Industries Research, Inc., Eagle Butte, SD, United States of America
| | - Lyle G Best
- Missouri Breaks Industries Research, Inc., Eagle Butte, SD, United States of America
| | - Kevin Francesconi
- Institute of Chemistry - Analytical Chemistry, University of Graz, Austria
| | - Walter Goessler
- Institute of Chemistry - Analytical Chemistry, University of Graz, Austria
| | - Poojitha Balakrishnan
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America
| | - Shelley A Cole
- Texas Biomedical Research Institute, San Antonio, TX, United States of America
| | - Mary V Gamble
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America
| | - Barbara V Howard
- MedStar Health Research Institute, Hyattsville, MD, United States of America; Department of Medicine, Georgetown University School of Medicine, Washington, DC, United States of America
| | - Ana Navas-Acien
- Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, NY, New York, United States of America; Department of Environmental Health & Engineering, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, United States of America
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Inoue T, Ishida T, Inoue T, Saito A, Ezura M, Uenohara H, Fujimura M, Sato K, Endo T, Omodaka S, Endo H, Niizuma K, Tominaga T. Lectin-Like Oxidized Low-Density Lipoprotein Receptor-1 Levels as a Biomarker of Acute Intracerebral Hemorrhage. J Stroke Cerebrovasc Dis 2018; 28:490-494. [PMID: 30442557 DOI: 10.1016/j.jstrokecerebrovasdis.2018.10.027] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Revised: 10/11/2018] [Accepted: 10/22/2018] [Indexed: 01/28/2023] Open
Abstract
BACKGROUND Correct diagnosis of cerebral stroke type, hemorrhagic or ischemic, is essential in the early stage to establish the optimum treatment. The diagnosis is mainly determined based on imaging studies. Other more available diagnostic methods are desirable, such as blood sample examination. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is very important in vascular dysfunction induced by oxidized low-density lipoprotein, including cell apoptosis. The present study evaluated LOX-1 as a biomarker for cerebral stroke. SUBJECTS AND METHODS Patients with newly diagnosed stroke were prospectively enrolled between February and July 2014. LOX-1 serum values were measured twice, within 24 hours and 2 months after the onset. RESULTS A total of 16 patients were enrolled; 7 patients with intracerebral hemorrhage (ICH) and 9 patients with cerebral infarction. Median LOX-1 values of patients with ICH and infarction in the acute phase were 1825.8 and 593.9 pg/mL, respectively, significantly higher in patients with ICH than in patients with infarction (P < .0001). CONCLUSION LOX-1 serum level has potential as a biomarker of ICH.
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Affiliation(s)
- Takashi Inoue
- Department of Neurosurgery, Sendai Medical Center, Sendai, Japan.
| | - Tomohisa Ishida
- Department of Neurosurgery, Sendai Medical Center, Sendai, Japan.
| | - Tomoo Inoue
- Department of Neurosurgery, Sendai Medical Center, Sendai, Japan.
| | - Atsushi Saito
- Department of Neurosurgery, Sendai Medical Center, Sendai, Japan.
| | - Masayuki Ezura
- Department of Neurosurgery, Sendai Medical Center, Sendai, Japan.
| | - Hiroshi Uenohara
- Department of Neurosurgery, Sendai Medical Center, Sendai, Japan.
| | - Miki Fujimura
- Department of Neurosurgery, Kohnan Hospital, Sendai, Japan.
| | - Kenichi Sato
- Department of Neurosurgery, Kohnan Hospital, Sendai, Japan.
| | - Toshiki Endo
- Department of Neurosurgery, Kohnan Hospital, Sendai, Japan.
| | | | - Hidenori Endo
- Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
| | - Kuniyasu Niizuma
- Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
| | - Teiji Tominaga
- Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
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Coimbra S, Reis F, Ferreira C, Nunes S, Viana S, Catarino A, Rocha-Pereira P, Belo L, Monteiro L, Catarino C, Santos-Silva A. Weight loss achieved by bariatric surgery modifies high-density lipoprotein subfractions and low-density lipoprotein oxidation towards atheroprotection. Clin Biochem 2018; 63:46-53. [PMID: 30342017 DOI: 10.1016/j.clinbiochem.2018.10.007] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2018] [Revised: 10/11/2018] [Accepted: 10/16/2018] [Indexed: 01/28/2023]
Abstract
OBJECTIVES Weight loss achieved by laparoscopic adjustable gastric banding (LAGB) induces an increase in high-density lipoprotein cholesterol (HDLc) but a small effect on low-density lipoprotein (LDL), although changes in their quality (size and composition) are uncertain. Our aim was to study the impact of weight loss, achieved 13-months after LAGB, on inflammation and dyslipidemia, focusing on HDL and LDL subfractions, and oxidized LDL (oxLDL). DESIGN & METHODS We evaluated standard lipid profile, HDL and LDL subfractions, oxLDL, interleukin (IL)-6 and C-reactive protein (CRP), in twenty obese patients, before (T0) and 13-months after LAGB (T1), and in seventeen healthy controls. RESULTS At T1, patients showed lower body weight (12% median weight loss) and anthropometric indices; reduction in TG, atherogenic indices, oxLDL, oxLDL/LDL ratio, CRP and IL-6, and enhancement in HDLc; an increase in large HDL and intermediate HDL subfractions, and a decrease in small HDL subfraction; LDL subfractions were not modified. Percentual change (%Δ) of oxLDL, from T0 to T1, correlated significantly and positively with %Δ of small HDL subfraction and with %Δ of body mass index. CONCLUSIONS Weight loss induced atheroprotective changes on inflammation, and lipid profile, enhancing larger HDL, the more atheroprotective subfraction, reducing the less protective subclass, small HDL, and reducing oxLDL and oxLDL/LDL ratio. Quality of lipoproteins appears useful cardiovascular risk biomarkers, deserving further studies.
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Affiliation(s)
- Susana Coimbra
- UCIBIO\REQUIMTE, Porto; CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra-Paredes, Portugal.
| | - Flávio Reis
- iCBR, Instituto de Investigação Clínica e Biomédica de Coimbra, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal
| | - Cátia Ferreira
- Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto (FFUP), Porto, Portugal
| | - Sara Nunes
- iCBR, Instituto de Investigação Clínica e Biomédica de Coimbra, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal
| | - Sofia Viana
- iCBR, Instituto de Investigação Clínica e Biomédica de Coimbra, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal; Instituto Politécnico de Coimbra, Escola Superior de Tecnologia da Saúde de Coimbra, Coimbra, Portugal
| | - Alice Catarino
- Hospital da Prelada-Dr. Domingos Braga da Cruz, Porto, Portugal
| | - Petronila Rocha-Pereira
- UCIBIO\REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto (FFUP), Porto, Portugal; Centro de Investigação em Ciências Saúde (CICS), Universidade da Beira Interior, Covilhã, Portugal
| | - Luís Belo
- UCIBIO\REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto (FFUP), Porto, Portugal
| | - Luís Monteiro
- Hospital da Prelada-Dr. Domingos Braga da Cruz, Porto, Portugal
| | - Cristina Catarino
- UCIBIO\REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto (FFUP), Porto, Portugal
| | - Alice Santos-Silva
- UCIBIO\REQUIMTE, Departamento de Ciências Biológicas, Laboratório de Bioquímica, Faculdade de Farmácia da Universidade do Porto (FFUP), Porto, Portugal.
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Kaur R, Kaur M, Singh J. Endothelial dysfunction and platelet hyperactivity in type 2 diabetes mellitus: molecular insights and therapeutic strategies. Cardiovasc Diabetol 2018; 17:121. [PMID: 30170601 PMCID: PMC6117983 DOI: 10.1186/s12933-018-0763-3] [Citation(s) in RCA: 408] [Impact Index Per Article: 58.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2018] [Accepted: 08/20/2018] [Indexed: 12/14/2022] Open
Abstract
The incidence and prevalence of diabetes mellitus is rapidly increasing worldwide at an alarming rate. Type 2 diabetes mellitus (T2DM) is the most prevalent form of diabetes, accounting for approximately 90-95% of the total diabetes cases worldwide. Besides affecting the ability of body to use glucose, it is associated with micro-vascular and macro-vascular complications. Augmented atherosclerosis is documented to be the key factor leading to vascular complications in T2DM patients. The metabolic milieu of T2DM, including insulin resistance, hyperglycemia and release of excess free fatty acids, along with other metabolic abnormalities affects vascular wall by a series of events including endothelial dysfunction, platelet hyperactivity, oxidative stress and low-grade inflammation. Activation of these events further enhances vasoconstriction and promotes thrombus formation, ultimately resulting in the development of atherosclerosis. All these evidences are supported by the clinical trials reporting the importance of endothelial dysfunction and platelet hyperactivity in the pathogenesis of atherosclerotic vascular complications. In this review, an attempt has been made to comprehensively compile updated information available in context of endothelial and platelet dysfunction in T2DM.
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Affiliation(s)
- Raminderjit Kaur
- Department of Molecular Biology & Biochemistry, Guru Nanak Dev University, Amritsar, Punjab, India
| | - Manpreet Kaur
- Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India
| | - Jatinder Singh
- Department of Molecular Biology & Biochemistry, Guru Nanak Dev University, Amritsar, Punjab, India.
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