Expression of microRNA-208 is associated with adverse clinical outcomes in human dilated cardiomyopathy.

Abstract

BACKGROUND:

Recently, microRNA-208 (miR-208) encoded by the alpha-myosin heavy chain (MHC) gene, has been shown to be involved in pathological cardiac growth, fibrosis, and up-regulation of beta-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 alpha-MHC mRNA were lower in patients with DCM than in controls, whereas beta-MHC mRNA levels were higher in patients with DCM compared with controls. Levels of miR-208 were correlated with beta-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.

• Authors: Mamoru Satoh, Yoshitaka Minami, Yuji Takahashi, Tsuyoshi Tabuchi, Motoyuki Nakamura
• Journal: Journal of cardiac failure (J Card Fail) Vol. 16 Issue 5 Pg. 404-10 (May 2010) ISSN: 1532-8414 [Electronic] United States
• PMID: 20447577 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MIRN499 microRNA, human
• MicroRNAs
• Collagen
• Ventricular Myosins
• Myosin Heavy Chains

Topics

• Cardiomyopathy, Dilated (genetics, mortality)
• Case-Control Studies
• Collagen (biosynthesis, genetics)
• Confidence Intervals
• Disease Progression
• Female
• Humans
• Japan
• Logistic Models
• Male
• MicroRNAs (biosynthesis, genetics)
• Middle Aged
• Multivariate Analysis
• Myosin Heavy Chains (genetics)
• Prognosis
• Risk
• Risk Factors
• Statistics as Topic
• Stroke Volume
• Treatment Outcome
• Ventricular Function, Left
• Ventricular Myosins (genetics)