Polymorphisms of Matrix Metalloproteinases in Systolic Heart Failure: Role on Disease Susceptibility, Phenotypic Characteristics, and Prognosis

Velho, Fábio Michalski; Cohen, Carolina Rodrigues; Santos, Kátia Gonçalves dos; Silvello, Daiane; Martinelli, Nidiane Carla; Biolo, Andréia; Clausell, Nadine Oliveira; Rohde, Luís Eduardo Paim

doi:10.1016/j.cardfail.2010.09.017

Cited by 19 publications

(23 citation statements)

References 31 publications

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“…In this scenario, allelic variants of the MMP-2 gene with reduced transcriptional activity would promote a diminished response to estradiol, thus reducing its beneficial effects on cardiac function, especially in HF patients (who already have structural and functional LV impairment). This could explain the seemingly paradoxical findings from previous studies that showed that patients carrying genotypes associated with higher expression of MMPs had a more favourable HF prognosis [25], and reduced LV mass index and LV end-diastolic diameter [46]. Overall, our data suggest that the TT genotype of the -790G>T polymorphism, putatively associated with increased MMP-2 gene expression, might be associated with decreased HF-related death rate in Caucasian-Brazilians.…”

Section: Discussionsupporting

confidence: 42%

“…At baseline, patients underwent a comprehensive clinical and biochemical evaluation consisting of physical examination, assessment of electro- and echocardiographic parameters, and laboratory exams. Ischemic etiology was defined as previously reported [25]. The prognostic end points were all-cause death and HF-related death, defined as sudden unexpected death (within 1 hour of onset of symptoms) or caused by advanced refractory disease.…”

Section: Methodsmentioning

confidence: 99%

“…We previously reported that the 2G allele of the MMP-1 –1607 1G/2G polymorphism was associated with better prognosis in patients with systolic HF [25]. We also showed that HF patients with the MMP-1 2G2G genotype and the 6A allele of the MMP-3 –1171 5A/6A polymorphism had increased QRS widening rate [26].…”

Section: Introductionmentioning

confidence: 98%

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Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival

et al. 2016

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Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285–0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365–1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248–1.093). Our study does not exclude the possibility that polymorphisms in MMP-2 gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies.

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Section: Discussionsupporting

confidence: 42%

Section: Methodsmentioning

confidence: 99%

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Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival

et al. 2016

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“…In contrast, there is no evidence for any effect of the MMP-3 genotype on cardiac events in patients with ischemic cardiomyopathy. 49 …”

Section: Mmps As Biomarkers For Heart Failurementioning

confidence: 99%

Matrix Metalloproteinases in Myocardial Infarction and Heart Failure

DeLeon‐Pennell

Meschiari

Jung

et al. 2017

Progress in Molecular Biology and Translational Science

213

188

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Cardiovascular disease (CVD) is the leading cause of death, accounting for 600,000 deaths each year in the U.S. In addition, heart failure accounts for 37% of healthcare spending. Matrix metalloproteinases (MMPs) increase after myocardial infarction (MI) and correlate with left ventricular dysfunction in heart failure patients. MMPs regulate the remodeling process by facilitating extracellular matrix (ECM) turnover and inflammatory signaling. Due to the critical role MMPs play during cardiac remodeling, there is a need to better understand the pathophysiological mechanism of MMPs, including the biological function of the downstream products of MMP proteolysis. Future studies developing new therapeutic targets that inhibit specific MMP actions to limit the development of heart failure post-MI are warranted. This book chapter focuses on the role of MMPs post-MI, the efficiency of MMPs as biomarkers for MI or heart failure, and the future of MMPs and their cleavage products as targets for prevention of post-MI heart failure.

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“…Ensaios futuros relevantes devem definir sua real indicação e importância na prática clínica. Certos polimorfismos da metaloproteinases podem estar associados a maior incidência de doença isquêmica e melhor prognóstico 18 .…”

Section: Troponina E Polimorfismounclassified

Atualização da Diretriz Brasileira de Insuficiência Cardíaca Crônica - 2012

2012

Arquivos Brasileiros De Cardiologia

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Polymorphisms of Matrix Metalloproteinases in Systolic Heart Failure: Role on Disease Susceptibility, Phenotypic Characteristics, and Prognosis

Cited by 19 publications

References 31 publications

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival

Matrix Metalloproteinase-2 Polymorphisms in Chronic Heart Failure: Relationship with Susceptibility and Long-Term Survival

Matrix Metalloproteinases in Myocardial Infarction and Heart Failure

Atualização da Diretriz Brasileira de Insuficiência Cardíaca Crônica - 2012

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