Role of myocardial MicroRNAs in the long-term ventricular remodelling of patients with aortic stenosis

Abstract

We hypothesize that miRs are key players in the dynamics of the hypertrophy phenotype in aortic stenosis (AS) patients. In our study, we aimed to identify the transcriptional patterns (protein-coding transcripts and miRs) from myocardial sample biopsies that could be associated with the absence of left ventricle (LV) mass regression after aortic valve replacement (AVR in patients with severe AS and LV hypertrophy. We prospectively included 40 patients with severe AS, LV hypertrophy and preserved EF undergoing AVR. Myocardial biopsies obtained during surgery were analysed for transcriptomic analysis performed by next generation sequencing. At a 1-year follow-up, no hypertrophy reversal was observed in about half of the patients in the absence of patient-prothesis mismatch, prosthesis dysfunction of uncontrolled hypertension. Predictors of mass regression were assessed From clinical, echocardiographic, biochemical variables as well as from 300 miRs obtained from myocardial specimens, allowing the identification 29 differentially expressed. miR 4709-3p was found as a positive independent predictor of hypertrophy regression together with hs-TNT as a negative predictor. Gene transcripts RFX1, SIX5, MAPK8IF3 and PKD1 were predicted as simultaneous targets of five upregulated miRs suggesting its importance in LV hypertrophy. In our cohort, tissue miR 4709-3p and hs-TNT were independent predictors of hypertrophy regression. The hypertrophy reversal process will likely depend from a complex network where miRNAs may have an important role, allowing a potential opportunity for therapy.