Arrhythmogenic right ventricular cardiomyopathy: implications of next-generation sequencing and of miRNAs regulation in appropriate understanding and treatment

We read the article by Medeiros-Domingo et al.1 with great interest and congratulate the authors on their excellent work. As the authors correctly state, currently, nearly 40% of the patients with an arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC) phenotype according to the task force 2010 criteria remain genetically elusive. By using whole-exome sequencing and analysing the protein coding exons and flanking splice sites of 96 genes associated with cardiomyopathies and channelopathies, they found rare genetic variants that may explain the phenotype in 64% of the cases.1 However, we would like to call attention to an aspect that needs further clarification. Research has also illustrated the importance of the genome-wide microRNA (miRNA) expression dysregulation in ARVC patients.2 There is evidence of both downregulation and upregulation of several miRNAs in ARVC heart tissues and that miR-21-5p and miR-135b are correlated with Wnt and Hippo pathway, involved in the molecular pathophysiology of ARVC. Furthermore, research has also reported that miR-21-5p and miR-135b are significantly associated with both the myocardium adipose and fibrosis, which was a potential disease pathway for ARVC and might to be useful as therapeutic targets for ARVC.2 The findings of Medeiros-Domingo et al.1 add significant informations to previously published data but also evaluating the real effect of the miRNAs regulation in ARVC would be useful for better understanding and treatment improving of the complex network of the ARVC. Conflict of interest: none declared.