Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy

Roberta Roncarati, Chiara Viviani Anselmi, Maria Angela Losi, Laura Papa, Elena Cavarretta, Paula Da Costa Martins, Carla Contaldi, Gloria Saccani Jotti, Anna Franzone, Laura Galastri, Michael V G Latronico, Massimo Imbriaco, Giovanni Esposito, Leon De Windt, Sandro Betocchi, Gianluigi Condorelli

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives The purpose of this paper was to determine whether microRNAs (miRNAs) involved in myocardial remodeling were differentially expressed in the blood of hypertrophic cardiomyopathy (HCM) patients, and whether circulating miRNAs correlated with the degree of left ventricular hypertrophy and fibrosis. Background miRNAs - small, noncoding ribonucleic acids (RNAs) that regulate gene expression by inhibiting RNA translation - modulate cellular function. Myocardial miRNAs modulate processes such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; non-CM-specific miRNAs regulate myocardial vascularization and fibrosis. Recently, the possibility that circulating miRNAs may be biomarkers of cardiovascular disease has been raised. Methods Forty-one HCM patients were characterized with conventional transthoracic echocardiography and cardiac magnetic resonance. Peripheral plasma levels of 21 miRNAs were assessed by quantitative real-time polymerase chain reaction and were compared with levels in a control group of 41 age- and sex-matched blood donors. Results Twelve miRNAs (miR-27a, -199a-5p, -26a, -145, -133a, -143, -199a-3p, -126-3p, -29a, -155, -30a, and -21) were significantly increased in HCM plasma. However, only 3 miRNAs (miR-199a-5p, -27a, and -29a) correlated with hypertrophy; more importantly, only miR-29a correlated also with fibrosis. Conclusions Our data suggest that cardiac remodeling associated with HCM determines a significant release of miRNAs into the bloodstream: the circulating levels of both cardiac- and non-cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with left ventricular hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, -27a, and -29a), whereas only miR-29a is significantly associated with both hypertrophy and fibrosis, identifying it as a potential biomarker for myocardial remodeling assessment in HCM.

Original languageEnglish
Pages (from-to)920-927
Number of pages8
JournalJournal of the American College of Cardiology
Volume63
Issue number9
DOIs
Publication statusPublished - Mar 11 2014

Keywords

  • circulating microRNAs
  • fibrosis
  • hypertrophic cardiomyopathy
  • myocardial remodeling

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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