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Sagheer U, Al-Kindi S, Abohashem S, Phillips CT, Rana JS, Bhatnagar A, Gulati M, Rajagopalan S, Kalra DK. Environmental Pollution and Cardiovascular Disease: Part 2 of 2: Soil, Water, and Other Forms of Pollution. JACC. ADVANCES 2024; 3:100815. [PMID: 38939394 PMCID: PMC11198458 DOI: 10.1016/j.jacadv.2023.100815] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/13/2023] [Accepted: 11/21/2023] [Indexed: 06/29/2024]
Abstract
With a growing body of evidence that now links environmental pollution to adverse cardiovascular disease (CVD) outcomes, pollution has emerged as an important risk factor for CVD. There is thus an urgent need to better understand the role of pollution in CVD, key pathophysiological mechanisms, and to raise awareness among health care providers, the scientific community, the general population, and regulatory authorities about the CV impact of pollution and strategies to reduce it. This article is part 2 of a 2-part state-of-the-art review on the topic of pollution and CVD-herein we discuss major environmental pollutants and their effects on CVD, highlighting pathophysiological mechanisms, and strategies to reduce CVD risk.
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Affiliation(s)
- Usman Sagheer
- Division of Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky, USA
| | - Sadeer Al-Kindi
- Division of Cardiology, Department of Medicine, University Hospitals, Harrington Heart and Vascular Institute, Case Western Reserve University, Cleveland, Ohio, USA
| | - Shady Abohashem
- Divison of Cardiovascular Imaging, Radiology Department, Massachusetts General Hospital-Harvard Medical School, Boston, Massachusetts, USA
| | - Colin T. Phillips
- Department of Cardiology, Maine Medical Center, Portland, Maine, USA
| | - Jamal S. Rana
- The Permanente Medical Group, Department of Cardiology, Oakland Medical Center, Oakland, California, USA
| | - Aruni Bhatnagar
- Division of Environmental Medicine, Department of Medicine, University of Louisville, Louisville, Kentucky, USA
| | - Martha Gulati
- Department of Cardiology, Barbra Streisand Women's Heart Center, Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
| | - Sanjay Rajagopalan
- Division of Cardiology, Department of Medicine, University Hospitals, Harrington Heart and Vascular Institute, Case Western Reserve University, Cleveland, Ohio, USA
| | - Dinesh K. Kalra
- Division of Cardiology, Department of Medicine, University of Louisville, Louisville, Kentucky, USA
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Liu Y, Guan S, Xu H, Zhang N, Huang M, Liu Z. Inflammation biomarkers are associated with the incidence of cardiovascular disease: a meta-analysis. Front Cardiovasc Med 2023; 10:1175174. [PMID: 37485268 PMCID: PMC10360053 DOI: 10.3389/fcvm.2023.1175174] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2023] [Accepted: 06/26/2023] [Indexed: 07/25/2023] Open
Abstract
Background Inflammation is a risk factor for cardiovascular disease (CVD), and particular inflammatory parameters can be used to predict the incidence of CVD. The aim of this study was to assess the association between fibrinogen (FIB), interleukin-6 (IL-6), C-reactive protein (CRP) and galectin-3 (Gal-3) and the risk of cardiovascular disease using meta-analysis. Methods PubMed, Embase, Scopus, and Web of Science databases were searched with the appropriate strategies to identify observational studies relevant to this meta-analysis. A random-effects model was used to combine inflammation factor-associated outcomes and cardiovascular disease outcomes, except in the case of galectin-3, where a fixed-effects model was used because of less heterogeneity. Location, age, type of cardiovascular disease, and sample size factors were used to explore heterogeneity in stratification and metaregression for subgroup analysis. A case-by-case literature exclusion approach was used for sensitivity analysis. The funnel plot and Begg's test were combined to assess publication bias. Results Thirty-three papers out of 11,456 were screened for inclusion in the analysis. Four inflammation biomarkers were significantly associated with the development of CVD: FIB (OR: 1.21, 95% CI: 1.15-1.27, P < 0.001; HR: 1.04, 95% CI: 1.00-1.07, P < 0.05), IL-6 (HR: 1.16, 95% CI: 1.10-1.22, P < 0.001), CRP (OR: 1.25, 95% CI: 1.15-1.35, P < 0.001; HR: 1.20, 95% CI: 1.14-1.25, P < 0.001) and Gal-3 (HR: 1.09, 95% CI: 1.05-1.14, P < 0.001). Location factors help explain the source of heterogeneity, and there is publication bias in the Gal-3 related literature. Conclusion Taken together, the current research evidence suggests that high levels of fibrinogen, interleukin-6, C-reactive protein and galectin-3 are risk factors for cardiovascular disease and can be used as biomarkers to predict the development of cardiovascular disease to some extent. Systematic Review Registration https://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023391844.
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Affiliation(s)
- Yifei Liu
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Suzhen Guan
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Haiming Xu
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Na Zhang
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Min Huang
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia, China
| | - Zhihong Liu
- School of Public Health, Ningxia Medical University, Yinchuan, China
- Key Laboratory of Environmental Factors and Chronic Disease Control, Ningxia Medical University, Yinchuan, Ningxia, China
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Aly K, Shaat M, Hamza S, Ali S. Triggers of Atrial Fibrillation in the Geriatric Medical Intensive Care Unit: An Observational Study. Cardiol Res 2023; 14:106-114. [PMID: 37091882 PMCID: PMC10116932 DOI: 10.14740/cr1461] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Accepted: 02/13/2023] [Indexed: 04/25/2023] Open
Abstract
Background Atrial fibrillation (AF) is a common arrhythmia in the non-cardiac intensive care unit (ICU). However, data concerning AF incidence and predictors in such populations are scarce and controversial. The study aimed to investigate the contributing factors of new-onset AF in elderly patients within the medical intensive care setting. Methods Patients admitted to ICU during a 6-month period were prospectively studied. Patients admitted for short period postoperative monitoring and patients with chronic or paroxysmal AF were excluded. The conditions involved as AF risk factors or "triggers" from demographic data, history, and echocardiography were recorded. Acute Physiology and Chronic Health Evaluation II score was calculated. Electrolytes including some trace elements (zinc, copper, and magnesium) were analyzed. Results The study included 142 patients (49% females). Mean age was 69.5 ± 7.3 years. AF was observed in 12%. Diagnosis of pneumonia (P < 0.001), low copper (P < 0.0001) and low zinc levels (P < 0.0001) was significantly associated with the occurrence of AF. By multivariate analysis, they remained statistically significant (odds ratio, 7.0; 95% confidence interval, 2.0 - 24.6; P < 0.01). Conclusions A significant fraction of ICU elderly patients manifests AF. The relevant factors contributing to AF incidence in the elderly are pneumonia and low zinc and low copper.
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Affiliation(s)
- Khaled Aly
- Cardiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
- Corresponding Author: Khaled Aly, Cardiology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt.
| | - Maram Shaat
- Geriatrics and Gerontology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Sarah Hamza
- Geriatrics and Gerontology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Safaa Ali
- Geriatrics and Gerontology Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt
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Khan N, Ullah J, Hashmi S, Ali A, Siddiqui AJ, Sami SA, Bokhari SS, Sharif H, Uddin J, El-Seedi HR, Musharraf SG. Dysregulation of metalloproteins in ischemic heart disease patients with systolic dysfunction. Int J Biol Macromol 2023; 232:123435. [PMID: 36716834 DOI: 10.1016/j.ijbiomac.2023.123435] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2022] [Revised: 01/10/2023] [Accepted: 01/22/2023] [Indexed: 01/29/2023]
Abstract
Ischemic heart disease (IHD) is the leading cause of mortality worldwide. Metalloproteins have been linked to human health and diseases. The molecular functions of metalloproteins in IHD is not well understood and require further exploration. The objective of this study was to find out the role of metalloproteins in the pericardial fluid of IHD patients having normal (EF > 45) and impaired (EF < 45) left ventricular ejection fraction (LVEF). IHD patients were grouped into two categories: LVEF<45 (n = 12) and LVEF >45 (n = 33). Pooled samples of pericardial fluid were fractionated by using ZOOM-isoelectric focusing (IEF) followed by further processing using one-dimensional gel electrophoresis (1D SDS-PAGE) and filter-aided sample preparation (FASP). Tryptic peptides of each fraction and differential bands were then analyzed by nano-LC-ESI-MS/MS. Protein identification was performed through a Mascot search engine using NCBI-Prot and SwissProt databases. A total of 1082 proteins including 154 metalloproteins were identified. In the differential bands, 60 metalloproteins were identified, while 115 metalloproteins were identified in all ZOOM-IEF fractions. Twelve differentially expressed metalloproteins were selected in the intense bands according to their molecular weight (MW) and isoelectric point (pI). The 12 differentially expressed metalloprotein includes ceruloplasmin, Prothrombin, Vitamin K-dependent protein, Fibulin-1, Ribosomal protein S6 kinase alpha-6, nidogen, partial, Serum albumin, Hemopexin, C-reactive protein, Serum amyloid P-component, and Intelectin-1 protein which were all up-regulated while serotransferrin is the only metalloprotein that was down-regulated in impaired (LVEF<45) group. Among the metalloproteins, Zn-binding proteins are 36.5 % followed by Ca-binging 32.2 %, and Fe-binging 12.2 %. KEGG, pathway analysis revealed the association of ceruloplasmin and serotransferrin with the ferroptosis pathway. In conclusion, 154 metalloproteins were identified of them the Zn-binding protein followed by Ca-binding and Fe-binding proteins were the most abundant metalloproteins. The two metalloproteins, the Cu-binding protein ceruloplasmin, and Fe-binding protein serotransferrin are involved in the ferroptosis pathway, an iron-dependent form of regulated cell death that has been linked to cardiac pathology, especially in IHD patients having impaired systolic (LVEF<45) dysfunction. However, further research is required to validate these findings.
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Affiliation(s)
- Noman Khan
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Junaid Ullah
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Satwat Hashmi
- Department of Biological and Biomedical Sciences, Agha Khan University, Karachi 74800, Pakistan
| | - Arslan Ali
- Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Amna Jabbar Siddiqui
- Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan
| | - Shahid Ahmed Sami
- Department of Surgery, The Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Syeda Saira Bokhari
- Department of Medicine, The Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Hasanat Sharif
- Department of Surgery, The Aga Khan University Hospital, Karachi 74800, Pakistan
| | - Jalal Uddin
- Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University, Asir 61421, Saudi Arabia
| | - Hesham R El-Seedi
- Pharmacognosy Group, Department of Pharmaceutical Biosciences, BMC, Uppsala University, SE-751 23 Uppsala, Sweden
| | - Syed Ghulam Musharraf
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan; Dr Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
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Podzolkov VI, Dragomiretskaya NA, Beliaev IG, Kucherova JS, Kazadaeva AV. Endothelial Microvascular Dysfunction and Its Relationship with Haptoglobin Levels in Patients with Different Phenotypes of Chronic Heart Failure. RATIONAL PHARMACOTHERAPY IN CARDIOLOGY 2021. [DOI: 10.20996/1819-6446-2021-10-05] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Aim. To study the relationship between the level of haptoglobin and the main indicators of microcirculation (MC) in patients with different phenotypes of chronic heart failure (CHF).Materials and methods. Patients with different phenotypes of functional class II-IV chronic heart failure according to NYHA (n=80) underwent a general clinical examination, determination of the serum haptoglobin level by enzyme-linked immunosorbent assay, as well as an assessment of the MC state on the medial surface of the upper third of the leg by laser Doppler flowmetry (LDF).Results. Patients with CHF included patients with preserved left ventricular ejection fraction (HFpEF; n=27, intermediate ejection fraction (HFmrEF; n=25) and reduced ejection fraction (HFrEF; n=28). The median value of haptoglobin in the HFpEF group was 1387.6 [ 747.5; 1946.9] mg/l, in the HFmrEF group was 1583.4 [818.9; 2201.4] mg/l, in the HFrEF group was 968.5 [509.5; 1324.4] mg/l. Correlation analysis revealed statistically significant relationships between haptoglobin and the amplitudes of the endothelial frequency range (Ae) in the groups of HFmrEF (r=-0.628, 95% confidence interval [CI] -0.256; -0.825, p=0.003) and HFrEF (r=-0.503, 95% CI -0.089; -0.803, p=0.02). A negative relationship between the haptoglobin level and Kv and σ was revealed, as well as a formula for calculating the value of haptoglobin was obtained, which is predicted on the basis of the amplitude index of the endothelial frequency range: [haptoglobin]=1787-(4053×Ae).Conclusion. The multifactorial effect of haptoglobin is realized in the central and peripheral mechanisms of MC regulation. Low values of haptoglobin in blood plasma should be considered as a potential marker for the development of complications and used in a comprehensive assessment of the state of patients with CHF. Evaluation of the diagnostic and prognostic significance of haptoglobin, especially in patients with HFmrEF, requires further study.
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Affiliation(s)
- V. I. Podzolkov
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | | | - I. G. Beliaev
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Ju. S. Kucherova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - A. V. Kazadaeva
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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Fibrinogen Level Predicts Outcomes in Critically Ill Patients with Acute Exacerbation of Chronic Heart Failure. DISEASE MARKERS 2021; 2021:6639393. [PMID: 34012493 PMCID: PMC8105095 DOI: 10.1155/2021/6639393] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 04/03/2021] [Accepted: 04/09/2021] [Indexed: 11/17/2022]
Abstract
Background Heart failure (HF) is a common cardiovascular disease, which is related to systemic inflammation for decades. Fibrinogen (FIB) is a sign of thrombosis and inflammation, which is associated with the prognosis of many diseases. Nevertheless, the role of fibrinogen level in the prognosis of critically ill patients with acute exacerbation of chronic heart failure is unclear. Methods The data are from the Medical Information Mart for Intensive Care III (MIMIC III) database, which is a freely accessible critical care database. The primary outcome in our study was 90-day mortality. The prognostic value of fibrinogen was analyzed with receiver operating characteristic (ROC) curve analysis, Kaplan-Meier curve, and Cox model. Results A total of 554 patients were included. Patients were divided into two groups, low fibrinogen level (<284 mg/dl) and high fibrinogen level (≥284 mg/dl), through the cut-off value of the ROC curve. The area under the ROC curve of fibrinogen for predicting 90-day mortality was 0.65 (95% CI: 0.59-0.70). In the unadjusted Cox model, compared with the low fibrinogen level (<284 mg/dl), the 90-day mortality of the hazard ratio (HR) with 95% confidence intervals (CI) of the high fibrinogen level is 3.33 (95% CI 2.15-5.15). In different multivariable Cox models, compared with the low fibrinogen level (<284 mg/dl), the 90-day mortality of the hazard ratio of the high fibrinogen level is from 2.83 to 3.13. In subgroup analyses, significant interactions were observed only in age, chronic kidney disease (CKD), and APS III scores. Conclusion Our data suggest that high fibrinogen levels (≥284 mg/dl) independently predict mortality in critically ill patients with acute exacerbation of chronic heart failure. Our findings need to be further validated by large prospective studies and longer follow-up time.
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McKechnie DG, Papacosta AO, Lennon LT, Welsh P, Whincup PH, Wannamethee SG. Inflammatory markers and incident heart failure in older men: the role of NT-proBNP. Biomark Med 2021; 15:413-425. [PMID: 33709785 PMCID: PMC8559131 DOI: 10.2217/bmm-2020-0669] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Aim: To determine the relationship between baseline inflammation (CRP and IL-6) with natriuretic peptide (NP) activity (measured by NT-proBNP) and incident heart failure (HF) in older men. Methods & results: In the British Regional Heart Study, 3569 men without prevalent myocardial infarction or HF were followed for mean 16.3 years; 327 developed HF. Baseline CRP and IL-6 were significantly and positively associated with NT-proBNP. Those in the highest CRP and IL-6 quartiles had an elevated risk of HF after age and BMI adjustment (HR = 1.42 [1.01–1.98] and 1.71 [1.24–2.37], respectively), which markedly attenuated after NT-proBNP adjustment (HR = 1.15 [0.81–1.63] and 1.25 [0.89–1.75], respectively). Conclusion: NP activity is associated with pro-inflammatory biomarkers and may explain the link between inflammation and incident HF. Inflammation describes the body’s natural response to infections, injuries and toxins. Inflammation is a helpful response in the short term, but it is thought that long-lasting inflammation – for example, due to illnesses such as diabetes or obesity – may have harmful effects. Previous studies have found that people with higher levels of inflammatory molecules in the blood seem to be more likely to develop heart failure (HF) later on. The amount of fluid in the body is controlled, in part, by molecules in the blood known as ‘natriuretic peptides' (NPs). People with HF have much higher levels of NPs in their blood, and these are used to help diagnose HF. There are suggestions that inflammation and natriuretic peptides are linked to one another. Using a sample of men aged 60–79 years, who did not have HF, we compared blood markers of inflammation and NPs at a baseline examination. Men with higher blood inflammatory markers tended to have higher blood NP levels. We then followed these men up for an average of 16.3 years. Men with higher blood inflammatory markers at baseline were more likely to develop HF, as expected, even after accounting for differences in age and BMI. However, when we accounted for NP levels at baseline, the increased risk of HF with inflammation disappeared. This suggests that NP activity is important in the relationship between inflammation and the risk of HF. Future studies should account for this when examining the link. It is possible that NPs or, more likely, whatever is driving their release, may explain why people with inflammation are more likely to get HF.
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Affiliation(s)
- Douglas Gj McKechnie
- Department of Primary Care & Population Health, University College London, London, UK
| | - A Olia Papacosta
- Department of Primary Care & Population Health, University College London, London, UK
| | - Lucy T Lennon
- Department of Primary Care & Population Health, University College London, London, UK
| | - Paul Welsh
- Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK
| | - Peter H Whincup
- Population Health Research Institute, St George's University of London, London, UK
| | - S Goya Wannamethee
- Department of Primary Care & Population Health, University College London, London, UK
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Romuk E, Jacheć W, Zbrojkiewicz E, Mroczek A, Niedziela J, Gąsior M, Rozentryt P, Wojciechowska C. Ceruloplasmin, NT-proBNP, and Clinical Data as Risk Factors of Death or Heart Transplantation in a 1-Year Follow-Up of Heart Failure Patients. J Clin Med 2020; 9:jcm9010137. [PMID: 31947878 PMCID: PMC7019681 DOI: 10.3390/jcm9010137] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2019] [Revised: 12/28/2019] [Accepted: 12/30/2019] [Indexed: 11/16/2022] Open
Abstract
We investigated whether the additional determination of ceruloplasmin (Cp) levels could improve the prognostic value of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in heart failure (HF) patients in a 1-year follow-up. Cp and NT-proBNP levels and clinical and laboratory parameters were assessed simultaneously at baseline in 741 HF patients considered as possible heart transplant recipients. The primary endpoint (EP) was a composite of all-cause death (non-transplant patients) or heart transplantation during one year of follow-up. Using a cut-off value of 35.9 mg/dL for Cp and 3155 pg/mL for NT-proBNP (top interquartile range), a univariate Cox regression analysis showed that Cp (hazard ratio (HR) = 2.086; 95% confidence interval (95% CI, 1.462–2.975)), NT-proBNP (HR = 3.221; 95% CI (2.277–4.556)), and the top quartile of both Cp and NT-proBNP (HR = 4.253; 95% CI (2.795–6.471)) were all risk factors of the primary EP. The prognostic value of these biomarkers was demonstrated in a multivariate Cox regression model using the top Cp and NT-proBNP concentration quartiles combined (HR = 2.120; 95% CI (1.233–3.646)). Lower left ventricular ejection fraction, VO2max, lack of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker therapy, and nonimplantation of an implantable cardioverter-defibrillator were also independent risk factors of a poor outcome. The combined evaluation of Cp and NT-proBNP had advantages over separate NT-proBNP and Cp assessment in selecting a group with a high 1-year risk. Thus multi-biomarker assessment can improve risk stratification in HF patients.
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Affiliation(s)
- Ewa Romuk
- Department of Biochemistry, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland
- Correspondence: ; Tel.: +48-322-722-318
| | - Wojciech Jacheć
- Second Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (W.J.); (C.W.)
| | - Ewa Zbrojkiewicz
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia, 40-055 Katowice, Poland; (E.Z.); (A.M.); (P.R.)
| | - Alina Mroczek
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia, 40-055 Katowice, Poland; (E.Z.); (A.M.); (P.R.)
| | - Jacek Niedziela
- 3rd Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Silesian Centre for Heart Disease, 41-800 Zabrze, Poland; (J.N.); (M.G.)
| | - Mariusz Gąsior
- 3rd Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Silesian Centre for Heart Disease, 41-800 Zabrze, Poland; (J.N.); (M.G.)
| | - Piotr Rozentryt
- Department of Toxicology and Health Protection, Faculty of Health Sciences in Bytom, Medical University of Silesia, 40-055 Katowice, Poland; (E.Z.); (A.M.); (P.R.)
- 3rd Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Silesian Centre for Heart Disease, 41-800 Zabrze, Poland; (J.N.); (M.G.)
| | - Celina Wojciechowska
- Second Department of Cardiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland; (W.J.); (C.W.)
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Gannon BM, Glesby MJ, Finkelstein JL, Raj T, Erickson D, Mehta S. A point-of-care assay for alpha-1-acid glycoprotein as a diagnostic tool for rapid, mobile-based determination of inflammation. CURRENT RESEARCH IN BIOTECHNOLOGY 2019; 1:41-48. [PMID: 32342042 PMCID: PMC7185229 DOI: 10.1016/j.crbiot.2019.09.002] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Inflammation is a key component of immune response to infections and pathogenesis of metabolic and cardiovascular diseases. Inflammatory biomarkers, including alpha-1-acid glycoprotein (AGP), are considered prognostic tools for predicting risk, monitoring response to therapy, and adjusting nutritional biomarkers for accurate interpretation. Serum is considered a primary source of biomarkers; urine and saliva are increasingly being explored and utilized as rapidly accessible, noninvasive biofluids requiring minimal sample processing and posing fewer biohazard risks. METHODS A lateral flow immunoassay was developed for an established mobile-based platform to quantify AGP in human serum, urine, and saliva. Assay performance was assessed with purified AGP in buffer, diluted human serum samples (n = 16) banked from a trial in people living with HIV, and saliva and urine (n = 15 each) from healthy participants. Reference methods were conventional clinical chemistry analyzer or commercial ELISA. Bootstrap analysis was used to train and validate sample calibration. FINDINGS The correlation between the assay and reference method for serum was 0.97 (P < 0.001). Mean (95% CI) best fit line slope was 1.0 (0.88, 1.15) and intercept was -0.003 (-0.08, 0.09). The correlation for urine was 0.93, and for saliva was 0.97 (both P < 0.001). The median CV for the LFIA for AGP in buffer was 13.2% and for all samples was 28.7%. INTERPRETATION The performance of the assay indicated potential use as a rapid, low sample volume input, and easy method to quantify AGP that can be licensed and adopted by commercial manufacturers for regulatory approvals and production. This has future applications for determining inflammatory status either alone or in conjunction with other inflammatory proteins such as C-reactive protein for prognostic, monitoring, or nutritional status applications, including large-scale country level surveys conducted by the DHS and those recommended by the WHO.
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Affiliation(s)
- Bryan M Gannon
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
- Institute for Nutritional Sciences, Global Health, and Technology (INSiGHT), Cornell University, Ithaca, NY, USA
| | - Marshall J Glesby
- Department of Medicine, Weill Cornell Medical College, New York, NY, USA
| | - Julia L Finkelstein
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
- Institute for Nutritional Sciences, Global Health, and Technology (INSiGHT), Cornell University, Ithaca, NY, USA
| | - Tony Raj
- Division of Nutrition, St. John’s Research Institute, Bangalore, India
| | - David Erickson
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
- Institute for Nutritional Sciences, Global Health, and Technology (INSiGHT), Cornell University, Ithaca, NY, USA
- Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, NY, USA
| | - Saurabh Mehta
- Division of Nutritional Sciences, Cornell University, Ithaca, NY, USA
- Institute for Nutritional Sciences, Global Health, and Technology (INSiGHT), Cornell University, Ithaca, NY, USA
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Li N, Zhou H, Tang Q. Red Blood Cell Distribution Width: A Novel Predictive Indicator for Cardiovascular and Cerebrovascular Diseases. DISEASE MARKERS 2017; 2017:7089493. [PMID: 29038615 PMCID: PMC5606102 DOI: 10.1155/2017/7089493] [Citation(s) in RCA: 159] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/17/2017] [Revised: 07/17/2017] [Accepted: 07/25/2017] [Indexed: 02/06/2023]
Abstract
The red blood cell distribution width (RDW) obtained from a standard complete blood count (CBC) is a convenient and inexpensive biochemical parameter representing the variability in size of circulating erythrocytes. Over the past few decades, RDW with mean corpuscular volume (MCV) has been used to identify quite a few hematological system diseases including iron-deficiency anemia and bone marrow dysfunction. In recent years, many clinical studies have proved that the alterations of RDW levels may be associated with the incidence and prognosis in many cardiovascular and cerebrovascular diseases (CVDs). Therefore, early detection and intervention in time of these vascular diseases is critical for delaying their progression. RDW as a new predictive marker and an independent risk factor plays a significant role in assessing the severity and progression of CVDs. However, the mechanisms of the association between RDW and the prognosis of CVDs remain unclear. In this review, we will provide an overview of the representative literatures concerning hypothetical and potential epidemiological associations between RDW and CVDs and discuss the underlying mechanisms.
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Affiliation(s)
- Ning Li
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China
- Hubei Key Laboratory of Cardiology, Wuhan 430060, China
| | - Heng Zhou
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China
- Hubei Key Laboratory of Cardiology, Wuhan 430060, China
| | - Qizhu Tang
- Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China
- Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China
- Hubei Key Laboratory of Cardiology, Wuhan 430060, China
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12
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Dysfunctional HDL in diabetes mellitus and its role in the pathogenesis of cardiovascular disease. Mol Cell Biochem 2017; 440:167-187. [PMID: 28828539 DOI: 10.1007/s11010-017-3165-z] [Citation(s) in RCA: 74] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/18/2017] [Accepted: 08/16/2017] [Indexed: 12/17/2022]
Abstract
Coronary artery disease, the leading cause of death in the developed and developing countries, is prevalent in diabetes mellitus with 68% cardiovascular disease (CVD)-related mortality. Epidemiological studies suggested inverse correlation between HDL and CVD occurrence. Therefore, low HDL concentration observed in diabetic patients compared to non-diabetic individuals was thought to be one of the primary causes of increased risks of CVD. Efforts to raise HDL level via CETP inhibitors, Torcetrapib and Dalcetrapib, turned out to be disappointing in outcome studies despite substantial increases in HDL-C, suggesting that factors beyond HDL concentration may be responsible for the increased risks of CVD. Therefore, recent studies have focused more on HDL function than on HDL levels. The metabolic environment in diabetes mellitus condition such as hyperglycemia-induced advanced glycation end products, oxidative stress, and inflammation promote HDL dysfunction leading to greater risks of CVD. This review discusses dysfunctional HDL as one of the mechanisms of increased CVD risks in diabetes mellitus through adversely affecting components that support HDL function in cholesterol efflux and LDL oxidation. The dampening of reverse cholesterol transport, a key process that removes cholesterol from lipid-laden macrophages in the arterial wall, leads to increased risks of CVD in diabetic patients. Therapeutic approaches to keep diabetes under control may benefit patients from developing CVD.
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13
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Corbo C, Molinaro R, Tabatabaei M, Farokhzad OC, Mahmoudi M. Personalized protein corona on nanoparticles and its clinical implications. Biomater Sci 2017; 5:378-387. [PMID: 28133653 PMCID: PMC5592724 DOI: 10.1039/c6bm00921b] [Citation(s) in RCA: 212] [Impact Index Per Article: 26.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
It is now well understood that once in contact with biological fluids, nanoscale objects lose their original identity and acquire a new biological character, referred to as a protein corona. The protein corona changes many of the physicochemical properties of nanoparticles, including size, surface charge, and aggregation state. These changes, in turn, affect the biological fate of nanoparticles, including their pharmacokinetics, biodistribution, and therapeutic efficacy. It is progressively being accepted that even slight variations in the composition of a protein source (e.g., plasma and serum) can substantially change the composition of the corona formed on the surface of the exact same nanoparticles. Recently it has been shown that the protein corona is strongly affected by the patient's specific disease. Therefore, the same nanomaterial incubated with plasma proteins of patients with different pathologies adsorb protein coronas with different compositions, giving rise to the concept of personalized protein corona. Herein, we review this concept along with recent advances on the topic, with a particular focus on clinical relevance.
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Affiliation(s)
- Claudia Corbo
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | - Roberto Molinaro
- Center for Biomimetic Medicine, Houston Methodist Research Institute, Houston, TX, USA
| | - Mateen Tabatabaei
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
| | - Omid C Farokhzad
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. and King Abdulaziz University, Jeddah 21589, Saudi Arabia
| | - Morteza Mahmoudi
- Center for Nanomedicine and Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. and Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
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14
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Agra RM, Varela-Román A, González-Ferreiro R, Viñuela JE, Castro-Pais A, Fernández-Trasancos Á, Díaz-Rodríguez E, Álvarez E, Carreira MC, Casanueva FF, González-Juanatey JR, Eiras S. Orosomucoid as prognosis factor associated with inflammation in acute or nutritional status in chronic heart failure. Int J Cardiol 2017; 228:488-494. [PMID: 27875723 DOI: 10.1016/j.ijcard.2016.11.134] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/22/2016] [Accepted: 11/06/2016] [Indexed: 12/17/2022]
Abstract
BACKGROUND Inflammation and nutritional state are involved in the pathogenesis of heart failure (HF). OBJECTIVE To study the contribution of alpha-1-acid-glycoprotein (AGP) to these factors and its prognostic value in acute (AHF) or chronic HF (CHF). METHODS The observational study has included 147 patients (mean age 70years, 62% men) admitted to a cardiology department for HF and followed-up for an average 326.6±140.8days. Blood AGP values were measured by Enzyme-Linked ImmunoSorbent Assay. Monocytes subsets were determined with CD14 and CD16 antibodies by flow cytometry and body composition was measured by dual-energy X-ray absorptiometry. The regulation of tumor necrosis factor (TNF-α) and leptin by AGP in epicardial adipose tissue (EAT) were analyzed by real time polymerase chain reaction. RESULTS High AGP, that was associated with CD14+CD16+ monocytes, and proBNP levels at the discharge were indicators of rehospitalization for HF in AHF patients. However, low AGP levels determined a worse nutritional state in CHF patients. The leptin levels were downregulated by high AGP concentration in epicardial fat. CONCLUSION AGP is a dual indicator in HF because high levels are predictors of adverse outcomes in AHF but low levels are related to the worse nutritional status in CHF. The regulation of leptin by AGP in epicardial fat might suggest a new pathway as protective mechanism in CHF.
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Affiliation(s)
- Rosa M Agra
- Cardiovascular Area and Coronary Unit, Complejo Hospitalario Universitario de Santiago de Compostela, Spain; Cardiology Group, Health Research Institute of Santiago de Compostela, Spain
| | - Alfonso Varela-Román
- Cardiovascular Area and Coronary Unit, Complejo Hospitalario Universitario de Santiago de Compostela, Spain; Cardiology Group, Health Research Institute of Santiago de Compostela, Spain
| | - Rocío González-Ferreiro
- Cardiovascular Area and Coronary Unit, Complejo Hospitalario Universitario de Santiago de Compostela, Spain
| | - Juan E Viñuela
- Immunology Unit, Complejo Hospitalario Universitario de Santiago de Compostela, Spain
| | - Ana Castro-Pais
- CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | | | | | - Ezequiel Álvarez
- Cardiology Group, Health Research Institute of Santiago de Compostela, Spain
| | - Marcos C Carreira
- CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Felipe F Casanueva
- CIBER Fisiopatología Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain; Laboratory of Molecular and Cellular Endocrinology, Department of Medicine, Endocrinology Division, University of Santiago de Compostela and Complejo Hospitalario Universitario, Santiago de Compostela, Spain
| | - José R González-Juanatey
- Cardiovascular Area and Coronary Unit, Complejo Hospitalario Universitario de Santiago de Compostela, Spain; Cardiology Group, Health Research Institute of Santiago de Compostela, Spain
| | - Sonia Eiras
- Cardiology Group, Health Research Institute of Santiago de Compostela, Spain.
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15
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Lage R, Moscoso I, Fernández-Trasancos Á, Cebro M, Couselo M, Fandiño-Vaquero R, Bravo SB, Sierra J, González-Juanatey JR, Eiras S. Differential behaviour of epicardial adipose tissue-secretomes with high and low orosomucoid levels from patients with cardiovascular disease in H9C2 cells. Mol Cell Endocrinol 2015; 416:77-87. [PMID: 26343163 DOI: 10.1016/j.mce.2015.08.025] [Citation(s) in RCA: 17] [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: 04/01/2015] [Revised: 08/26/2015] [Accepted: 08/26/2015] [Indexed: 11/26/2022]
Abstract
Epicardial adipose tissue releases orosomucoid (ORM), an acute phase protein with multiple modulatory and protective properties. We aimed to identify the effect of EAT-supernatants according to their ORM levels on H9C2 cells. H9C2 were cultured with EAT-secretomes or ORM protein itself on a Real-Time Cell Analyser. Secretome proteins identification was performed by LC-mass spectrometry according to their ORM levels. Two of them were validated by ELISA in EAT-supernatants from 42 patients. ORM effect on H9C2 and neonatal rat cardiomyocytes apoptosis under hypoxia with or without fatty acid treatment was determined by Annexin-V flow cytometry measurement. Caspase-3 expression levels were determined by western blot in H9C2. Our results showed a differential effect of EAT-secretomes according their ORM levels. Although additional secreted proteins can contribute to their beneficial effects, ORM reduced hypoxia-induced apoptosis through caspase-3 inhibition. Our data showed the cardioprotective role of ORM and suggest that its quantification on EAT secretomes might help us to find new secreted factors with a cardioprotective role.
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Affiliation(s)
- Ricardo Lage
- Cardiology Group, Health Research Institute, University Clinical Hospital of Santiago de Compostela, Spain; Cardiovascular Area, Center for Research in Molecular Medicine and Chronic Diseases of Santiago de Compostela, University Clinical Hospital of Santiago de Compostela, Spain
| | - Isabel Moscoso
- Cardiology Group, Health Research Institute, University Clinical Hospital of Santiago de Compostela, Spain; Cardiovascular Area, Center for Research in Molecular Medicine and Chronic Diseases of Santiago de Compostela, University Clinical Hospital of Santiago de Compostela, Spain
| | - Ángel Fernández-Trasancos
- Cardiology Group, Health Research Institute, University Clinical Hospital of Santiago de Compostela, Spain
| | - María Cebro
- Cardiovascular Area, Center for Research in Molecular Medicine and Chronic Diseases of Santiago de Compostela, University Clinical Hospital of Santiago de Compostela, Spain
| | - Marinela Couselo
- Cardiovascular Area, Center for Research in Molecular Medicine and Chronic Diseases of Santiago de Compostela, University Clinical Hospital of Santiago de Compostela, Spain
| | - Rubén Fandiño-Vaquero
- Department of Cardiology and Coronary Unit, University Clinical Hospital of Santiago de Compostela, Spain
| | - Susana B Bravo
- Proteomic Unit, University Clinical Hospital of Santiago de Compostela, Spain
| | - Juan Sierra
- Department of Heart Surgery, University Clinical Hospital of Santiago de Compostela, Spain
| | - José Ramón González-Juanatey
- Cardiology Group, Health Research Institute, University Clinical Hospital of Santiago de Compostela, Spain; Cardiovascular Area, Center for Research in Molecular Medicine and Chronic Diseases of Santiago de Compostela, University Clinical Hospital of Santiago de Compostela, Spain; Department of Cardiology and Coronary Unit, University Clinical Hospital of Santiago de Compostela, Spain
| | - Sonia Eiras
- Cardiology Group, Health Research Institute, University Clinical Hospital of Santiago de Compostela, Spain.
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16
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Borné Y, Persson M, Melander O, Smith JG, Engström G. Increased plasma level of soluble urokinase plasminogen activator receptor is associated with incidence of heart failure but not atrial fibrillation. Eur J Heart Fail 2015; 16:377-83. [PMID: 24464777 DOI: 10.1002/ejhf.49] [Citation(s) in RCA: 53] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 11/08/2013] [Accepted: 11/15/2013] [Indexed: 11/10/2022] Open
Abstract
AIMS Soluble urokinase plasminogen activator receptor (suPAR) in plasma is a novel inflammatory marker thought to be released from the cell surface of neutrophils, T cells, and macrophages. Other inflammatory markers, mainly acute phase proteins produced in the liver, have been associated with the incidence of heart failure (HF) and atrial fibrillation (AF). We investigated the association between suPAR and incident HF and AF in a population-based cohort. METHODS AND RESULTS Soluble urokinase plasminogen activator receptor was measured in 4530 subjects (aged 46–68 years, 61% women), who participated in the Malmö Diet and Cancer study during 1991–1996. Incident cases of HF and AF were identified from the Swedish hospital discharge register during a median follow-up of 16.3 years. During follow-up, 109 subjects (55% men) were diagnosed with new-onset HF and 321 individuals (50% men) with AF. suPAR was significantly associated with increased plasma levels of NT-proBNP (P<0.001). suPAR was significantly associated with incidence of HF [hazard ratio (HR) for the third vs. first tertile 3.33, 95% confidence interval (CI) 1.91–5.81 after adjustment for age and sex; and HR 1.82, 95% CI 1.02–3.27, P for trend 0.018 after adjustment for conventional risk factors and biomarkers]. suPAR was significantly associated with incidence of AF, when adjusted for age and sex (HR 1.40, 95% CI 1.06–1.85). However, this relationship was non-significant after adjustment for conventional risk factors and biomarkers. CONCLUSION Soluble urokinase plasminogen activator receptor was associated with increased plasma levels of NT-proBNP and incidence of HF, but not with AF among middle-aged subjects.
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17
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Raghban A, Kirsop J, Tang WHW. Prevention of Heart Failure in Patients with Chronic Kidney Disease. CURRENT CARDIOVASCULAR RISK REPORTS 2015; 9:428. [PMID: 38993263 PMCID: PMC11238633 DOI: 10.1007/s12170-014-0428-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/24/2022]
Abstract
Patients with chronic kidney disease (CKD) have heightened risk of developing heart failure (HF), yet few clinical studies have directly investigated the pathophysiologic underpinnings or therapeutic strategies to prevent HF. A wide range of clinically available cardiac and renal biomarkers can identify at-risk individuals who would benefit from dietary and lifestyle modifications (exercise prescription, smoking cessation), as well as risk factor modification (blood pressure, glucose, and lipid control). Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have the most consistent data for risk reduction, while other standard HF drugs such as beta-blockers and mineralocorticoid receptor antagonists have promising findings but no large-scale clinical trial evidence for their routine use to prevent the development and progression of HF in this vulnerable population.
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Affiliation(s)
- Amr Raghban
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA
| | - Jennifer Kirsop
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA
| | - W H Wilson Tang
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA
- Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-4, Cleveland, OH 44195, USA
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18
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Hammadah M, Fan Y, Wu Y, Hazen SL, Tang WHW. Prognostic value of elevated serum ceruloplasmin levels in patients with heart failure. J Card Fail 2014; 20:946-52. [PMID: 25128745 PMCID: PMC4250410 DOI: 10.1016/j.cardfail.2014.08.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2014] [Revised: 07/23/2014] [Accepted: 08/07/2014] [Indexed: 10/24/2022]
Abstract
BACKGROUND Ceruloplasmin (Cp) is a copper-binding acute-phase protein that is increased in inflammatory states and deficient in Wilson's disease. Recent studies demonstrate that increased levels of Cp are associated with increased risk of developing heart failure. Our objective was to test the hypothesis that serum Cp provides incremental and independent prediction of survival in stable patients with heart failure. METHODS AND RESULTS We measured serum Cp levels in 890 patients with stable heart failure undergoing elective cardiac evaluation that included coronary angiography. We examined the role of Cp levels in predicting survival over 5 years of follow-up. Mean Cp level was 26.6 ± 6.9 mg/dL and demonstrated relatively weak correlation with B-type natriuretic peptide (BNP; r = 0.187; P < .001). Increased Cp levels were associated with increased 5-year all-cause mortality (quartile [Q] 4 vs Q1 hazard ratio [HR] 1.9, 95% confidence interval [CI] 1.4-2.8; P < .001). When controlled for coronary disease traditional risk factors, creatinine clearance, dialysis, body mass index, medications, history of myocardial infarction, BNP, left ventricular ejection fraction (LVEF), heart rate, QRS duration, left bundle branch blockage, and implantable cardioverter-defibrillator placement, higher Cp remained an independent predictor of increased mortality (Q4 vs Q1 HR 1.7, 95% CI 1.1-2.6; P < .05). Model quality was improved with addition of Cp to the aforementioned covariables (net reclassification improvement of 9.3%; P < .001). CONCLUSIONS Ceruloplasmin is an independent predictor of all-cause mortality in patients with heart failure. Measurement of Cp may help to identify patients at heightened mortality risk.
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Affiliation(s)
- Muhammad Hammadah
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio
| | - Yiying Fan
- Department of Mathematics, Cleveland State University, Cleveland, Ohio
| | - Yuping Wu
- Department of Mathematics, Cleveland State University, Cleveland, Ohio
| | - Stanley L Hazen
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - W H Wilson Tang
- Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio; Department of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
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A novel BET bromodomain inhibitor, RVX-208, shows reduction of atherosclerosis in hyperlipidemic ApoE deficient mice. Atherosclerosis 2014; 236:91-100. [DOI: 10.1016/j.atherosclerosis.2014.06.008] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2013] [Revised: 05/29/2014] [Accepted: 06/16/2014] [Indexed: 01/12/2023]
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20
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Adamsson Eryd S, Sjögren M, Smith JG, Nilsson PM, Melander O, Hedblad B, Engström G. Ceruloplasmin and atrial fibrillation: evidence of causality from a population-based Mendelian randomization study. J Intern Med 2014; 275:164-71. [PMID: 24118451 DOI: 10.1111/joim.12144] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
OBJECTIVES Inflammatory diseases and inflammatory markers secreted by the liver, including C-reactive protein (CRP) and ceruloplasmin, have been associated with incident atrial fibrillation (AF). Genetic studies have not supported a causal relationship between CRP and AF, but the relationship between ceruloplasmin and AF has not been studied. The purpose of this Mendelian randomization study was to explore whether genetic polymorphisms in the gene encoding ceruloplasmin are associated with elevated ceruloplasmin levels, and whether such genetic polymorphisms are also associated with the incidence of AF. DESIGN Genetic polymorphisms in the ceruloplasmin gene (CP) were genotyped in a population-based cohort study of men from southern Sweden (Malmö Preventive Project; n = 3900). Genetic polymorphisms associated with plasma ceruloplasmin concentration were also investigated for association with incident AF (n = 520) during a mean follow-up of 29 years in the same cohort. Findings were replicated in an independent case-control sample (The Malmö AF cohort; n = 2247 cases, 2208 controls). RESULTS A single nucleotide polymorphism (rs11708215, minor allele frequency 0.12) located in the CP gene promoter was strongly associated with increased levels of plasma ceruloplasmin (P = 9 × 10(-10) ) and with AF in both the discovery cohort [hazard ratio 1.24 per risk allele, 95% confidence interval (CI) 1.06-1.44, P = 0.006] and the replication cohort (odds ratio 1.13, 95% CI 1.02-1.26, P = 0.02). CONCLUSIONS Our findings indicate a causal role of ceruloplasmin in AF pathophysiology and suggest that ceruloplasmin might be a mediator in a specific inflammatory pathway that causally links inflammatory diseases and incidence of AF.
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Affiliation(s)
- S Adamsson Eryd
- Department of Clinical Sciences, Lund University, Malmö, Sweden
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Adamsson Eryd S, Borné Y, Melander O, Persson M, Smith JG, Hedblad B, Engström G. Red blood cell distribution width is associated with incidence of atrial fibrillation. J Intern Med 2014; 275:84-92. [PMID: 24112470 DOI: 10.1111/joim.12143] [Citation(s) in RCA: 83] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
OBJECTIVES Red blood cell distribution width (RDW), a measure of variation in erythrocyte volume, has been associated with several cardiovascular disorders, but the relationship with atrial fibrillation (AF) remains unclear. We investigated the association between RDW and incidence of first hospitalization due to AF in a population-based cohort. DESIGN Red blood cell distribution width was measured in 27,124 subjects from the general population (age 45-73 years, 62% women) with no history of AF, heart failure, myocardial infarction or stroke. The association between baseline RDW and incidence of AF identified from the Swedish Hospital Discharge Register was evaluated. RESULTS During a mean follow-up of 13.6 years, 1894 subjects (53% men) were hospitalized with a diagnosis of AF. After adjustment for potential confounding factors, including cardiovascular disease risk factors, nutrient intake (iron, vitamin B12 and folate) and several haematological parameters (haemoglobin concentration, mean corpuscular volume and corpuscular haemoglobin content), the hazard ratio (HR) for incidence of AF was 1.33 [95% confidence interval (CI) 1.16-1.53] for the fourth versus first quartile of RDW (P for trend <0.001). The results were essentially unchanged when subjects with incident myocardial infarction or hospitalizations because of heart failure were censored from the analysis (HR 1.30, 95% CI 1.13-1.51; P for trend = 0.001). CONCLUSION Red blood cell distribution width was associated with incidence of AF independently of several cardiovascular, nutritional and haematological factors in this study of middle-aged subjects from the general population.
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Affiliation(s)
- S Adamsson Eryd
- Department of Clinical Sciences, Lund University, Malmö , Sweden
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Association of a prothrombotic state with left-ventricular diastolic dysfunction in hypertension. J Hypertens 2013; 31:2077-84. [DOI: 10.1097/hjh.0b013e328362d951] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
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Gravez B, Tarjus A, Jimenez-Canino R, El Moghrabi S, Messaoudi S, de la Rosa DA, Jaisser F. The diuretic torasemide does not prevent aldosterone-mediated mineralocorticoid receptor activation in cardiomyocytes. PLoS One 2013; 8:e73737. [PMID: 24040049 PMCID: PMC3767808 DOI: 10.1371/journal.pone.0073737] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2013] [Accepted: 07/23/2013] [Indexed: 01/16/2023] Open
Abstract
Aldosterone binds to the mineralocorticoid receptor (MR) and exerts pleiotropic effects beyond enhancing renal sodium reabsorption. Excessive mineralocorticoid signaling is deleterious during the evolution of cardiac failure, as evidenced by the benefits provided by adding MR antagonists (MRA) to standard care in humans. In animal models of cardiovascular diseases, MRA reduce cardiac fibrosis. Interestingly diuretics such as torasemide also appear efficient to improve cardiovascular morbidity and mortality, through several mechanisms. Among them, it has been suggested that torasemide could block aldosterone binding to the MR. To evaluate whether torasemide acts as a MRA in cardiomyocytes, we compared its effects with a classic MRA such as spironolactone. We monitored ligand-induced nuclear translocation of MR-GFP and MR transactivation activity in the cardiac-like cell line H9C2 using a reporter gene assay and known endogenous aldosterone-regulated cardiac genes. Torasemide did not modify MR nuclear translocation. Aldosterone-induced MR transactivation activity was reduced by the MRA spironolactone, not by torasemide. Spironolactone blocked the induction by aldosterone of endogenous MR-responsive genes (Sgk-1, PAI-1, Orosomucoid-1, Rgs-2, Serpina-3, Tenascin-X), while torasemide was ineffective. These results show that torasemide is not an MR antagonist; its association with MRA in heart failure may however be beneficial, through actions on complementary pathways.
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Affiliation(s)
- Basile Gravez
- INSERM Unité 872, Université Pierre et Marie Curie, Team 1, Centre de Recherche des Cordeliers, Paris, France
| | - Antoine Tarjus
- INSERM Unité 872, Université Pierre et Marie Curie, Team 1, Centre de Recherche des Cordeliers, Paris, France
| | - Ruben Jimenez-Canino
- Department of Physiology and Institute of Biomedical Technologies, Universidad de La Laguna, Tenerife, Spain
| | - Soumaya El Moghrabi
- INSERM Unité 872, Université Pierre et Marie Curie, Team 1, Centre de Recherche des Cordeliers, Paris, France
| | - Smail Messaoudi
- INSERM Unité 872, Université Pierre et Marie Curie, Team 1, Centre de Recherche des Cordeliers, Paris, France
| | - Diego Alvarez de la Rosa
- Department of Physiology and Institute of Biomedical Technologies, Universidad de La Laguna, Tenerife, Spain
| | - Frederic Jaisser
- INSERM Unité 872, Université Pierre et Marie Curie, Team 1, Centre de Recherche des Cordeliers, Paris, France
- Centre d’ Investigation Clinique, Institut Lorrain du Coeur et des Vaisseaux, Centre Hospitalier Universitaire de Brabois, Vandoeuvre-lès-Nancy, France
- * E-mail:
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Dadu RT, Dodge R, Nambi V, Virani SS, Hoogeveen RC, Smith NL, Chen F, Pankow JS, Guild C, Tang WHW, Boerwinkle E, Hazen SL, Ballantyne CM. Ceruloplasmin and heart failure in the Atherosclerosis Risk in Communities study. Circ Heart Fail 2013; 6:936-43. [PMID: 23861484 DOI: 10.1161/circheartfailure.113.000270] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
BACKGROUND Ceruloplasmin (Cp) decreases nitric oxide bioavailability in blood and has been associated with cardiovascular disease (CVD) in clinical studies. We assessed the associations between Cp and incident heart failure (HF), death, and CVD in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS Cp was measured at ARIC visit 4 (1996-1998). We studied 9240 individuals without HF or CVD at ARIC visit 4 and followed them for a mean of 10.5 years. Genome-wide association study was performed to identify genetic determinants of Cp levels and evaluate their association with incident HF in ARIC participants. Cp levels (mean±SD) were higher in women versus men (335±79 versus 258±44 mg/L; P<0.0001), women on versus not on hormone-replacement therapy (398±89 versus 291±60 mg/L; P<0.0001), and African Americans versus whites (299±63 versus 293±74 mg/L; P=0.0005). After adjusting for traditional risk factors, high-sensitivity C-reactive protein, N-terminal pro-B-type natriuretic peptide, and high-sensitivity cardiac troponin T, higher levels of Cp were associated with HF (hazard ratio, 1.44; 95% confidence interval, 1.13-1.83) and mortality (hazard ratio, 1.38; 95% confidence interval, 1.11-1.63). A locus on the ceruloplasmin gene on chromosome 3 was significantly associated with Cp levels (normal 295.56±77.60 mg/L; heterozygote 316.72±88.02 mg/L; homozygote 331.04±85.40 mg/L; P=8.3×10(-13)) but not with incident HF. After adjustment for traditional risk factors, Cp levels were also weekly associated with CVD. CONCLUSIONS Cp was associated with incident HF, mortality, and CVD in the ARIC population. A single locus on chromosome 3 was associated with Cp levels but not with HF.
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Borné Y, Hedblad B, Essén B, Engström G. Anthropometric measures in relation to risk of heart failure hospitalization: a Swedish population-based cohort study. Eur J Public Health 2012. [DOI: 10.1093/eurpub/cks161] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
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Shahabi P, Siest G, Herbeth B, Ndiaye NC, Visvikis-Siest S. Clinical necessity of partitioning of human plasma haptoglobin reference intervals by recently-discovered rs2000999. Clin Chim Acta 2012; 413:1618-24. [DOI: 10.1016/j.cca.2012.04.033] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2012] [Revised: 04/23/2012] [Accepted: 04/29/2012] [Indexed: 11/28/2022]
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Borné Y, Engström G, Essén B, Hedblad B. Immigrant status and increased risk of heart failure: the role of hypertension and life-style risk factors. BMC Cardiovasc Disord 2012; 12:20. [PMID: 22443268 PMCID: PMC3325899 DOI: 10.1186/1471-2261-12-20] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2011] [Accepted: 03/26/2012] [Indexed: 11/16/2022] Open
Abstract
Background Studies from Sweden have reported association between immigrant status and incidence of cardiovascular diseases. The nature of this relationship is unclear. We investigated the relationship between immigrant status and risk of heart failure (HF) hospitalization in a population-based cohort, and to what extent this is mediated by hypertension and life-style risk factors. We also explored whether immigrant status was related to case-fatality after HF. Methods 26,559 subjects without history of myocardial infarction (MI), stroke or HF from the community-based Malmö Diet and Cancer (MDC) cohort underwent a baseline examination during 1991-1996. Incidence of HF hospitalizations was monitored during a mean follow-up of 15 years. Results 3,129 (11.8%) subjects were born outside Sweden. During follow-up, 764 subjects were hospitalized with HF as primary diagnosis, of whom 166 had an MI before or concurrent with the HF. After adjustment for potential confounding factors, the hazard ratios (HR) for foreign-born were 1.37 (95% CI: 1.08-1.73, p = 0.009) compared to native Swedes, for HF without previous MI. The results were similar in a secondary analysis without censoring at incident MI. There was a significant interaction (p < 0.001) between immigrant status and waist circumference (WC), and the increased HF risk was limited to immigrants with high WC. Although not significant foreign-born tended to have lower one-month and one-year mortality after HF. Conclusions Immigrant status was associated with long-term risk of HF hospitalization, independently of hypertension and several life-style risk factors. A significant interaction between WC and immigrant status on incident HF was observed.
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Affiliation(s)
- Yan Borné
- Department of Clinical Sciences, Cardiovascular Epidemiology, Skåne University Hospital, Lund University, Malmö, Sweden.
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Stenman LK, Holma R, Korpela R. High-fat-induced intestinal permeability dysfunction associated with altered fecal bile acids. World J Gastroenterol 2012; 18:923-9. [PMID: 22408351 PMCID: PMC3297051 DOI: 10.3748/wjg.v18.i9.923] [Citation(s) in RCA: 147] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2011] [Revised: 09/20/2011] [Accepted: 01/18/2012] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigate whether high-fat-feeding is associated with increased intestinal permeability via alterations in bile acid metabolism.
METHODS: Male C57Bl/6J mice were fed on a high-fat (n = 26) or low-fat diet (n = 24) for 15 wk. Intestinal permeability was measured from duodenum, jejunum, ileum and colon in an Ussing chamber system using 4 kDa FITC-labeled dextran as an indicator. Fecal bile acids were analyzed with gas chromatography. Segments of jejunum and colon were analyzed for the expression of farnesoid X receptor (FXR) and tumor necrosis factor (TNF).
RESULTS: Intestinal permeability was significantly increased by high-fat feeding in jejunum (median 0.334 for control vs 0.393 for high-fat, P = 0.03) and colon (0.335 for control vs 0.433 for high-fat, P = 0.01), but not in duodenum or ileum. The concentration of nearly all identified bile acids was significantly increased by high-fat feeding (P < 0.001). The proportion of ursodeoxycholic acid (UDCA) in all bile acids was decreased (1.4% ± 0.1% in high-fat vs 2.8% ± 0.3% in controls, P < 0.01) and correlated inversely with intestinal permeability (r = -0.72, P = 0.01). High-fat feeding also increased jejunal FXR expression, as well as TNF expression along the intestine, especially in the colon.
CONCLUSION: High-fat-feeding increased intestinal permeability, perhaps by a mechanism related to bile acid metabolism, namely a decreased proportion of fecal UDCA and increased FXR expression.
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Speciation of trace elements in human serum by micro anion exchange chromatography coupled with inductively coupled plasma mass spectrometry. Anal Biochem 2012; 421:16-25. [DOI: 10.1016/j.ab.2011.11.004] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2011] [Revised: 10/03/2011] [Accepted: 11/05/2011] [Indexed: 11/22/2022]
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Hermsdorff HHM, Volp ACP, Puchau B, Barbosa KBF, Zulet MA, Bressan J, Martínez JA. Contribution of gender and body fat distribution to inflammatory marker concentrations in apparently healthy young adults. Inflamm Res 2012; 61:427-35. [PMID: 22258089 DOI: 10.1007/s00011-011-0429-z] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2011] [Revised: 08/24/2011] [Accepted: 12/23/2011] [Indexed: 12/22/2022] Open
Abstract
OBJECTIVE This cross-sectional study assessed the potential contribution of gender, body fat distribution, and their interactions to some inflammatory marker concentrations [C-reactive protein (CRP), complement factor 3 (C3), and ceruloplasmin (Cp)] in young adults. METHODS Measurements included body composition, lifestyle features, blood biochemical and selected inflammatory markers on 317 healthy subjects [122 males/195 females; 22 ± 3 years; 22.1 ± 2.8 kg/m(2) (mean ± SD)]. RESULTS Women had significantly higher CRP and Cp concentrations than men. No gender difference was noted in C3 concentrations. In a multivariate model of the whole sample, body fat (BF), waist circumference (WC) and the sex × WC interaction term presented the highest R (2) for variance of CRP (11%), C3 (2%), and Cp (12%), respectively. In regression models separated by sex, BF was the adiposity indicator that explained the variability of CRP in men (13%) and women (7%). WC was the only variable significantly associated with C3 concentrations in women (3%). BF presented the highest partial R (2) for Cp in men (8%) and WC in women (16%). CONCLUSION Our findings indicate a relevant interaction between gender and body fat distribution on the variance of CRP, C3, and Cp concentrations in apparently healthy young adults.
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Affiliation(s)
- Helen Hermana M Hermsdorff
- Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona, Spain
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Tewari AK, Popova-Butler A, El-Mahdy MA, Zweier JL. Identification of differentially expressed proteins in blood plasma of control and cigarette smoke-exposed mice by 2-D DIGE/MS. Proteomics 2011; 11:2051-62. [PMID: 21500341 DOI: 10.1002/pmic.201000159] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2010] [Revised: 02/04/2011] [Accepted: 02/11/2011] [Indexed: 01/23/2023]
Abstract
Cigarette smoke exposure is known to induce obstructive lung disease and several cardiovascular disease states in humans and also in animal models. Smoking leads to oxidative stress and inflammation that are important in triggering pulmonary and cardiovascular disease. The objective of the current study was to quantify differences in expression levels of plasma proteins of cigarette smoke -exposed and control mice, at the time of disease onset, and identify these proteins for use as potential biomarkers of the onset of smoking-induced disease. We utilized 2-D DIGE/MS to characterize these proteomic changes. 2-D DIGE of plasma samples identified 11 differentially expressed proteins in cigarette smoke -exposed mice. From these 11 proteins, 9 were downregulated and 2 were upregulated. The proteins identified are involved in vascular function, coagulation, metabolism and immune function. Among these, the alterations in fibrinogen (2.2-fold decrease), α-1-antitrypsin (1.8-fold increase) and arginase (4.5-fold decrease) are of particular interest since these have been directly linked to cardiovascular and lung pathology. Differences in expression levels of these proteins were also confirmed by immunoblotting. Thus, we observe that chronic cigarette smoke exposure in mice leads to prominent changes in the protein expression profile of blood plasma and these changes in turn can potentially serve as markers predictive of the onset and progression of cardiovascular and pulmonary disease.
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Affiliation(s)
- Arun K Tewari
- Center for Environmental and Smoking Induced Disease, Davis Heart and Lung Research Institute, Division of Cardiovascular Medicine, Department of Internal Medicine, Ohio State University College of Medicine, Columbus, OH 43210-1252, USA
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Inflammation-sensitive proteins and risk of atrial fibrillation: a population-based cohort study. Eur J Epidemiol 2011; 26:449-55. [DOI: 10.1007/s10654-011-9565-6] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2010] [Accepted: 03/04/2011] [Indexed: 10/18/2022]
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Puerta A, Díez-Masa JC, Martín-Álvarez PJ, Martín-Ventura JL, Barbas C, Tuñón J, Egido J, de Frutos M. Study of the capillary electrophoresis profile of intact α-1-acid glycoprotein isoforms as a biomarker of atherothrombosis. Analyst 2011; 136:816-22. [DOI: 10.1039/c0an00320d] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
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Hsueh SK, Wu CJ, Fang HY, Hsieh YK, Fang CY, Chen CJ, Chen SM, Yang CH, Yip HK, Chen MC, Fu M, Cheng CI. Comparison of Drug-Eluting Stent With Bare Metal Stent for Distal De Novo Unprotected Left Main Coronary Artery Stenosis - A Propensity Score-Matched Cohort Study -. Circ J 2011; 75:290-8. [DOI: 10.1253/circj.cj-10-0468] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
Affiliation(s)
- Shu-Kai Hsueh
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Chiung-Jen Wu
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Hsiu-Yu Fang
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Yuan-Kai Hsieh
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Chih-Yuan Fang
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Chien-Jen Chen
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Shyh-Ming Chen
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Cheng-Hsu Yang
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Hon-Kan Yip
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Mien-Cheng Chen
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Morgan Fu
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
| | - Cheng-I Cheng
- Chang Gung University College of Medicine
- Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung Medical Center
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Birdsall RE, Kiley MP, Segu ZM, Palmer CD, Madera M, Gump BB, MacKenzie JA, Parsons PJ, Mechref Y, Novotny MV, Bendinskas KG. Effects of lead and mercury on the blood proteome of children. J Proteome Res 2010; 9:4443-53. [PMID: 20681587 PMCID: PMC2935177 DOI: 10.1021/pr100204g] [Citation(s) in RCA: 26] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Abstract
Heavy metal exposure in children has been associated with a variety of physiological and neurological problems. The goal of this study was to utilize proteomics to enhance the understanding of biochemical interactions responsible for the health problems related to lead and mercury exposure at concentrations well below CDC guidelines. Blood plasma and serum samples from 34 children were depleted of their most abundant proteins using antibody-based affinity columns and analyzed using two different methods, LC-MS/MS and 2-D electrophoresis coupled with MALDI-TOF/MS and tandem mass spectrometry. Apolipoprotein E demonstrated an inverse significant association with lead concentrations (average being one microgram/deciliter) as deduced from LC-MS/MS and 2-D electrophoresis and confirmed by Western blot analysis. This coincides with prior findings that Apolipoprotein E genotype moderates neurobehavioral effects in individuals exposed to lead. Fifteen other proteins were identified by LC-MS/MS as proteins of interest exhibiting expressional differences in the presence of environmental lead and mercury.
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Affiliation(s)
| | | | - Zaneer M. Segu
- METACyt Biochemical Analysis Center, Department of Chemistry,
Indiana University, 800 E Kirkwood Ave., Bloomington, IN 47405
| | - Christopher D. Palmer
- Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, New
York State Department of Health, Albany, NY 12201
| | - Milan Madera
- METACyt Biochemical Analysis Center, Department of Chemistry,
Indiana University, 800 E Kirkwood Ave., Bloomington, IN 47405
| | | | | | - Patrick J. Parsons
- Laboratory of Inorganic and Nuclear Chemistry, Wadsworth Center, New
York State Department of Health, Albany, NY 12201
- Department of Environmental Health Sciences, School of Public
Health, University at Albany, State University of New York, Albany, NY 12201
| | - Yehia Mechref
- METACyt Biochemical Analysis Center, Department of Chemistry,
Indiana University, 800 E Kirkwood Ave., Bloomington, IN 47405
| | - Milos V. Novotny
- METACyt Biochemical Analysis Center, Department of Chemistry,
Indiana University, 800 E Kirkwood Ave., Bloomington, IN 47405
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Yan RT, Fernandes V, Yan AT, Cushman M, Redheuil A, Tracy R, Vogel-Claussen J, Bahrami H, Nasir K, Bluemke DA, Lima JAC. Fibrinogen and left ventricular myocardial systolic function: The Multi-Ethnic Study of Atherosclerosis (MESA). Am Heart J 2010; 160:479-86. [PMID: 20826256 PMCID: PMC2937158 DOI: 10.1016/j.ahj.2010.06.001] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/26/2009] [Accepted: 06/04/2010] [Indexed: 02/07/2023]
Abstract
BACKGROUND Increasing evidence suggests that elevated plasma fibrinogen is associated with incident heart failure. However, the underlying pathophysiological mechanisms have not been well elucidated. METHODS We examined the relationship between plasma fibrinogen level and peak systolic midwall circumferential strain (Ecc) at the base, mid cavity, and apex of the left ventricle measured by magnetic resonance imaging myocardial tagging in 1096 participants without clinical cardiovascular disease enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA). RESULTS After adjustment for demographics, established risk factors and body mass index, elevated fibrinogen was independently associated with reductions in absolute Ecc indicative of impaired systolic function in all regions (all P < or = .015). The relationships were consistently significant upon further adjustment for measures of atherosclerosis (all P < .024) and were modestly attenuated with regional heterogeneity after additional adjustment for other inflammatory biomarker and N-terminal pro-brain natriuretic peptide. In this fully-adjusted model, every 1-SD (74 mg/dL) increment in plasma fibrinogen was independently associated with a reduction in left ventricular absolute Ecc of 0.29% (95% CI 0.03%-0.59%, P = .048) at the base, 0.22% (95% CI 0.006%-0.43%, P = .044) at mid cavity, 0.20% (95% CI = -0.035% to 0.43%, P = .097) at the apex, and 0.24% (95% CI = 0.05%-0.43%, P = .015) overall. CONCLUSIONS Among asymptomatic individuals without clinical cardiovascular disease, elevated fibrinogen is independently associated with impaired myocardial systolic function. These findings support roles of inflammation, procoagulation, and hyperviscosity underlying hyperfibrinogenemia in the pathogenesis of incipient myocardial dysfunction.
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Affiliation(s)
- Raymond T Yan
- Johns Hopkins Hospital, Baltimore, MD 21287-0409, USA
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Bassi N, Zampieri S, Ghirardello A, Tonon M, Zen M, Cozzi F, Doria A. Pentraxins, anti-pentraxin antibodies, and atherosclerosis. Clin Rev Allergy Immunol 2009; 37:36-43. [PMID: 19016000 DOI: 10.1007/s12016-008-8098-6] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
Atherosclerosis is a disease of the vascular wall, which predominantly affects large and medium-sized arteries. It represents a leading cause of morbidity and mortality in the Western world. In the last few decades, it has been clearly shown that immune system plays a relevant role in atherogenesis. The effectors of both innate and adaptive immunity, including immune cells, cell or soluble receptors, cytokines, chemokines, complement components or coagulation systems, and autoantibodies are able to modulate atherosclerosis. Among proteins belonging to innate immunity, the highly conserved pentraxin family, which encompass C-reactive protein (CRP), serum amyloid P (SAP), and the long pentraxin 3 (PTX3) seems to be directly involved in the induction and progression of atherosclerosis. By immunohistochemical staining, pentraxins were found within the atherosclerotic plaques where they could play a key role interacting with atherogenic-modified lipoproteins, favoring the formation of foam cells, and exerting a proinflammatory action. Pentraxin serum levels have been shown to be associated with clinical and subclinical atherosclerosis in general population. Antibodies against pentraxins have been demonstrated in patients with autoimmune diseases, but their role in atherogenesis is still controversial.
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Affiliation(s)
- N Bassi
- Department of Medical and Surgical Sciences, University of Padova, Via Giustiniani, 2, 35128, Padova, Italy
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Engström G, Melander O, Hedblad B. Carotid intima-media thickness, systemic inflammation, and incidence of heart failure hospitalizations. Arterioscler Thromb Vasc Biol 2009; 29:1691-5. [PMID: 19644052 DOI: 10.1161/atvbaha.109.193490] [Citation(s) in RCA: 28] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
OBJECTIVE This study explored the relationships between carotid intima-media thickness (IMT), plasma levels of C-reactive protein (CRP), and incidence of heart failure hospitalizations. METHODS AND RESULTS Men and women from the general population (n=4691), without history of myocardial infarction or stroke, were examined. Incidence of hospitalizations attributable to heart failure was studied over a mean follow-up of 13 years. A total of 75 subjects were hospitalized with a primary diagnosis of heart failure. Adjusted for risk factors, the hazards ratios (95% CI) were 1.00, 0.98 (0.36 to 2.7), 1.9 (0.80 to 4.6), and 2.7 (1.1 to 6.2), respectively, for the 1st, 2nd, 3rd, and 4th quartiles of IMT (P for trend=0.003). The HR associated with CRP levels >or=3 mg/L (versus <1 mg/L) was 2.0 (95% CI: 1.06 to 3.9) after adjustments for risk factors. There was a significant interaction between IMT and CRP on heart failure incidence (P=0.028). Subjects with CRP >or=3 mg/L and IMT in the 4th quartile had an adjusted HR of 3.7 (1.9 to 7.1) compared to those with CRP <3 mg/L and IMT in quartile 1 to 3. CONCLUSIONS High IMT and high CRP are both independent risk factors for incidence of heart failure requiring hospitalization. The joint exposure to both risk factors substantially increases the risk.
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Affiliation(s)
- Gunnar Engström
- Department of Clinical Sciences in Malmö, Lund University, Malmö University Hospital, Sweden.
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von Haehling S, Schefold JC, Lainscak M, Doehner W, Anker SD. Inflammatory Biomarkers in Heart Failure Revisited: Much More than Innocent Bystanders. Heart Fail Clin 2009; 5:549-60. [DOI: 10.1016/j.hfc.2009.04.001] [Citation(s) in RCA: 83] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
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Sen U, Tyagi N, Patibandla PK, Dean WL, Tyagi SC, Roberts AM, Lominadze D. Fibrinogen-induced endothelin-1 production from endothelial cells. Am J Physiol Cell Physiol 2009; 296:C840-7. [PMID: 19193866 DOI: 10.1152/ajpcell.00515.2008] [Citation(s) in RCA: 48] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
We previously demonstrated that fibrinogen (Fg) binding to the vascular endothelial intercellular adhesion molecule-1 (ICAM-1) leads to microvascular constriction in vivo and in vitro. Although a role of endothelin-1 (ET-1) in this Fg-induced vasoconstriction was suggested, the mechanism of action was not clear. In the current study, we tested the hypothesis that Fg-induced vasoconstriction results from ET-1 production by vascular endothelial cells (EC) and is mediated by activation of extracellular signal-regulated kinase -1/2 (ERK-1/2). Confluent, rat heart microvascular endothelial cells (RHMECs) were treated with one of the following: Fg (2 or 4 mg/ml), Fg (4 mg/ml) with ERK-1/2 kinase inhibitors (PD-98059 or U-0126), Fg (4 mg/ml) with an antibody against ICAM-1, or medium alone for 45 min. The amount of ET-1 formed and the concentration of released von Willebrand factor (vWF) in the cell culture medium were measured by ELISAs. Fg-induced exocytosis of Weibel-Palade bodies (WPBs) was assessed by immunocytochemistry. Phosphorylation of ERK-1/2 was detected by Western blot analysis. Fg caused a dose-dependent increase in ET-1 formation and release of vWF from the RHMECs. This Fg-induced increase in ET-1 production was inhibited by specific ERK-1/2 kinase inhibitors and by anti-ICAM-1 antibody. Immunocytochemical staining showed that an increase in Fg concentration enhanced exocytosis of WPBs in ECs. A specific endothelin type B receptor blocker, BQ-788, attenuated the enhanced phosphorylation of ERK-1/2 in ECs caused by increased Fg content in the culture medium. The presence of an endothelin converting enzyme inhibitor, SM-19712, slightly decreased Fg-induced phosphorylation of ERK-1/2, but inhibited production of Fg-induced ET-1 production. These results suggest that Fg-induced vasoconstriction may be mediated, in part, by activation of ERK-1/2 signaling and increased production of ET-1 that further increases EC ERK-1/2 signaling. Thus, an increased content of Fg may enhance vasoconstriction through increased production of ET-1.
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Affiliation(s)
- Utpal Sen
- Dept. of Physiology, Univ. of Louisville, School of Medicine, Bldg. A, Rm. 1115, 500 South Preston St., Louisville, KY 40202, USA
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