MicroRNAs (miRNAs) have become potential targets for the treatment of heart failure (HF). It has been shown that miR-1 can reverse cardiac hypertrophy during the compensatory phase of HF development, but it is unknown whether miR-1 can still reverse cardiac dysfunction and improve cardiac remodeling after HF progresses to the decompensation stage. We established a mouse model of isoproterenol-induced HF and then injected miR-1a-3p agomir (agomir-1) into the tail vein. Echocardiography showed that the mice treated with agomir-1 had significantly increased ejection fraction and fractional shortening. These mice also showed a decrease in the N-terminal pro-B type natriuretic peptide (NT-proBNP) levels, but this remained higher than in controls. Cardiac hypertrophy, myocardial fibrosis, apoptosis, and glycogen deposition were reduced in mice treated with agomir-1. Furthermore, we found that supplementation of agomir-1 increased the expression of two mitochondrial DNA-encoded proteins, mitochondrially encoded NADH dehydrogenase 1 (ND1) and mitochondrially encoded cytochrome c oxidase I (COX1). In conclusion, our study found that miR-1a-3p alleviated the symptoms of ISO-induced HF in mice by enhancing mitochondrial ND1 and COX1. The results of this work may provide new therapeutic strategies for the treatment of HF patients.
Keywords: COX1; Heart failure; MiR-1; ND1; Therapy.
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