Carvedilol Alters Circulating MiR-1 and MiR-214 in Heart Failure

MicroRNAs (miRNAs) are recognized as major contributors in various cardiovascular diseases, such as heart failure (HF). These small noncoding RNAs that posttranscriptionally 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.

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.

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).

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.