MicroRNAs have been associated with cardiomyocyte apoptosis, a process involved in myocardial remodelling in aortic valve (Av) stenosis (AS). Our aim was to analyse whether the dysregulation of myocardial microRNAs was related to cardiomyocyte apoptosis in AS patients. Endomyocardial biopsies were obtained from 28 patients with severe AS (based on pressure gradients and Av area) referred to Av replacement and from necropsies of 10 cardiovascular disease-free control subjects. AS patients showed an increased ( P <0.001) cardiomyocyte apoptotic index (CMAI) compared with controls. Two clusters of patients were identified according to the CMAI: group 1 (CMAI≤0.08%; n=16) and group 2 (CMAI>0.08%; n=12). Group 2 patients presented lower cardiomyocyte density ( P <0.001) and ejection fraction ( P <0.05), and higher troponin T levels ( P <0.05), prevalence of heart failure ( P <0.05) and NT-proBNP levels ( P <0.05) than those from group 1. MicroRNA expression profile analysed in 5 patients randomly selected from each group showed 64 microRNAs down-regulated and 6 up-regulated ( P <0.05) in group 2 compared to group 1. Those microRNAs with the highest fold-change were validated in the full 2 groups corroborating that miR-10b, miR-125b-2* and miR-338-3p were down-regulated ( P <0.05) in group 2 compared with group 1 and control subjects. These 3 microRNAs were inversely correlated ( P <0.05) with the CMAI. Inhibition of miR-10b induced an increase ( P <0.05) of apoptosis and increased expression ( P <0.05) of Apaf-1 in HL-1 cardiomyocytes. In conclusion, myocardial down-regulation of miR-10b may be involved in increased cardiomyocyte apoptosis in AS patients, probably through Apaf-1 upregulation, contributing to cardiomyocyte damage and to the development of heart failure.
- aortic valve stenosis
- cardiomyocyte apoptosis
- heart failure
- ©2016 The Author(s)
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