Abstract 8831: Micro RNA Could Play Key Roles in Progression of Myocardial Fibrosis in Patients with Heart Failure
Purpose: MicroRNAs (miRNAs) are recently discovered, posttranscriptional regulators of gene expression. Roles of miRNAs in the development of heart failure are largely unknown. Myocardial fibrosis had been fully demonstrated to be involved in pathogenesis of heart failure. However, the molecular mechanisms that underlie myocardial fibrosis remain incompletely understood. We hypothesized that miRNAs might play key roles in the pathogenesis of myocardial fibrosis in patients with heart failure, resulting in progression of heart failure.
Methods: This study comprised of 22 patients with idiopathic dilated cardiomyopathy (DCM). We first performed a genome-wide miRNA expression profiling for a total of 650 miRNAs using endomyocardial biopsy specimens obtained from 8 patients. We used the median value of collagen volume fraction (CVF) in endomyocardial biopsy specimens as cutoff to divide these 8 patients into 2 groups. From this screening study, we selected 7 miRNAs related to myocardial fibrosis. We then performed real-time PCR in endomyocardial biopsy specimens from remaining 14 patients with DCM to quantify these 7 miRNAs expressions.
Results: In the first screening study, 7 miRNAs were differentially expressed significantly (p < 0.01) in 4 patients with severe myocardial fibrosis compared with 4 patients with less severe myocardial fibrosis (CVF: 4.4 ± 0.9 vs. 2.3 ± 0.3 %, respectively). The real-time PCR in endomyocardial biopsy specimens from remaining 14 patients with DCM revealed that expressions of miRNA-1, miRNA-23, miRNA-210, and miRNA-624 were significantly reduced in 7 patients with severe fibrosis compared with 7 with less severe fibrosis (CVF: 5.8 ± 1.3 vs. 2.0 ± 1.0 %, respectively).
Conclusion: We demonstrated that 4 specific miRNAs could play key roles in myocardial fibrosis in patients with DCM. These findings could provide insight into a key conundrum that pervades pathogenesis of heart failure.
- © 2011 by American Heart Association, Inc.