Abstract

miRNAs are a class of over 5000 noncoding RNAs that regulate more than half of the protein-encoding genes by provoking their degradation or preventing their translation. miRNAs are key regulators of complex biological processes underlying several cardiovascular disorders, including left ventricular hypertrophy, ischemic heart disease, heart failure, hypertension and arrhythmias. Moreover, circulating miRNAs herald promise as biomarkers in acute myocardial infarction and heart failure. In this context, this review gives an overview of studies that suggest that miRNAs could also play a role in valvular heart diseases. This area of research is still at its infancy, and further investigations in large patient cohorts and cellular or animal models are needed to provide strong data. Most studies focused on aortic stenosis, one of the most common valvular diseases in developed countries. Profiling and functional analyses indicate that miRNAs could contribute to activation of aortic valve interstitial cells to a myofibroblast phenotype, leading to valvular fibrosis and calcification, and to pressure overload-induced myocardial remodeling and hypertrophy. Data also indicate that specific miRNA signatures, in combination with clinical and functional imaging parameters, could represent useful biomarkers of disease progression or recovery after aortic valve replacement.

Highlights

  • Valvular heart disease (VHD) is a major leading cause of cardiovascular mortality

  • The present review aims at giving an overview on current knowledge of the role of miRNAs in the most common VHDs

  • High expression of miR-21 correlated with mean transvalvular gradient and left ventricular (LV) fibrosis, and miR-378 levels correlated with LV mass index. miR-1 was associated with LV hypertrophy (LVH) and correlated with levels of soluble heart-type fatty acid-binding protein-3 (FABP3), a lipid-binding protein and main target of peroxisome proliferator-activated receptor γ (PPARγ). miR-378 was an indepedent predictor of LVH, while miR-133a predicted LVH reversibility one year after surgery

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Summary

Introduction

Valvular heart disease (VHD) is a major leading cause of cardiovascular mortality. According to the most recent statistics, the prevalence of any VHD in the entire U.S population is 2.7%, with 0.4% aortic stenosis, 0.5% aortic regurgitation, 0.1% mitral stenosis, and 1.7% mitral regurgitation [1]. Prevalence of VHD increases with age, reaching about 13% in patients ě75 years old [2]

Aortic Stenosis
Mitral Valve Disorders
Aortic Valves
Left Ventricle
Mitral Valve Disease
Atrium
Mitral Valves
Methods
46 AS patients requiring AVR
Circulating miRNA
Findings
Roles of miRNAs in VHD
Conclusions

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