Circulating miR-29a, Among Other Up-Regulated MicroRNAs, Is the Only Biomarker for Both Hypertrophy and Fibrosis in Patients With Hypertrophic Cardiomyopathy

Objectives To determine whether microRNAs (miRNA) involved in myocardial remodeling were differentially expresse 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 non-coding 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 trans-thoracic echocardiography and cardiac magnetic resonance (CMR). Peripheral plasma levels of 21 miRNAs were assessed by quantitative real-time PCR and compared with those in a control group of 41 age- and sex-matched blood donors. Results Twelve miRNAs (miR-27a, miR-199a-5p, miR-26a, miR-145, miR-133a, miR-143, miR-199a-3p, miR-126-3p, miR-29a, miR-155, miR-30a, and miR-21) were significantly increased in HCM plasma. However, only three miRNAs (miR-199a-5p, miR-27a, and miR-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-specific and non-cardiac-specific miRNAs are significantly increased in the plasma of HCM patients. However, correlation with LV hypertrophy parameters holds true for only a few miRNAs (i.e., miR-199a-5p, miR-27a, and miR-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.