Carvedilol alters circulating mir-1 and mir-214 in heart failure

Abstract

Introduction: MicroRNAs (miRNAs) are recognized as major contributors in various cardiovascular diseases, such as heart failure (HF). These small noncoding RNAs that posttranscrip-tionally control target genes are involved in regulating different pathophysiological processes including cardiac proliferation, ifferentiation, hypertrophy, and fibrosis. Although carvedilol, a β-adrenergic blocker, and a drug of choice in HF produce cytoprotective actions against cardiomyocyte hypertrophy, the mechanisms are poorly understood. Here we proposed that the expression of hypertrophic-specific miRNAs (miR-1, miR-133, miR-208, and miR-214) might be linked to beneficial effects of carvedilol. Methods: The levels of four hypertrophic-specific miRNAs were measured in the sera of 35 patients with systolic HF receiving carvedilol (treated) and 20 HF patients not receiving any β-blockers (untreated) as well as 17 nonHF individuals (healthy) using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Systolic HF was defined as left ventricular ejection fraction <50% by transthoracic echocardiography. Results: We demonstrated that miR-1 and miR-214 were significantly upregulated in the treated group compared to the untreated group (P=0.014 and 5.3-fold, 0.033 and 4.2-fold, respectively). However, miR-133 and miR-208 did not show significant difference in expression between these two study groups. MiR-1 was significantly downregulated in the untreated group compared with healthy individuals (P=0.019 and 0.14-fold). Conclusion: In conclusion, it might be postulated that one of the mechanisms by which carvedilol may exert its cardioprotective effects can be through increasing miR-1 and miR-214 expressions which may also serve as a potential therapeutic target in patients with systolic HF in future.