Regulation by bisoprolol for cardiac microRNA expression in a rat volume-overload heart failure model.

Emerging evidence suggests the involvement of altered microRNA (miRNA) regulation in heart failure pathogenesis. We established a rat volume-overload heart failure model, and examined miRNA expression in normal rats and in the heart failure model, both with and without treatment with bisoprolol. Using miRNA microarrays, we identified 46 differentially expressed miRNAs in the rat heart failure model compared with normal rats. We also identified 18 differentially expressed miRNAs following treatment of normal rats with bisoprolol. Treatment with bisoprolol reversed, to varying degrees, the expression of 10 of the 46 miRNAs whose expression was differentially expressed in the heart failure model. Bioinformatic category analysis of the predicted target genes of these 10 miRNAs suggested that several encode ion-binding proteins. Our results showed that bisoprolol intervention can significantly improve cardiac function and decrease myocardial reconstruction in chronic heart failure. These data suggest that the expression of many miRNAs changes during heart failure, and that bisoprolol may exert its cardioprotective effects in part by reversing the differential expression of some of these genes.