Expression of microRNA-208 is Associated With Adverse Clinical Outcomes in Human Dilated Cardiomyopathy

Abstract 

Background

Recently, microRNA-208 (miR-208) encoded by the α-myosin heavy chain (MHC) gene, has been shown to be involved in pathological cardiac growth, fibrosis, and up-regulation of β-MHC expression. A recent study has also reported 2 additional myosin-expressed miRNAs (miR-208b and miR-499). The aim of this study was to determine whether miR-208, miR-208b, and miR-499 are expressed with MHC mRNA in human dilated cardiomyopathy (DCM), and whether these levels are related to left ventricular (LV) function and to clinical outcomes.

Methods and Results

Endomyocardial biopsy tissues were obtained from 82 patients with DCM and 21 subjects without LV dysfunction as controls. Levels of miR-208, miR-208b, and miR-499 were higher in DCM patients than in controls. Levels of α-MHC mRNA were lower in patients with DCM than in controls, whereas β-MHC mRNA levels were higher in patients with DCM compared with controls. Levels of miR-208 were correlated with β-MHC mRNA levels and myocardial collagen volume, whereas levels of miR-208b and miR-499 showed no correlation. After a mean follow-up of 517 days, an increase in miR-208 levels was shown to be a strong predictor of clinical outcomes (RR 3.4, 95% CI 1.1–11.2).

Conclusions

This study suggests that myocardial expression of miR-208 is associated with MHC mRNA expression and with poor clinical outcomes in patients with DCM. We conclude that miR-208 may therefore be involved in the progression of human DCM.

Key Words: Biopsy, collagen volume, heart failure, myosin heavy chains