SIRT1-dependent regulation of mitochondrial metabolism participates in miR-30a-5p-mediated cardiac remodeling post-myocardial infarction.

Abstract

Myocardial infarction-triggered myocardial remodeling is fatal for therapies. The miR-30 family is an essential component of several physiological and pathological processes. Previous studies have proved that the miR-30 family may contribute to regulating myocardial infarction. This study aimed to demonstrate that the combination of miR-30a-5p and mitochondrial metabolism recapitulates the critical features for remodeling post-myocardial infarction. Using gain- and loss-of-function of miR-30a-5p in mice, we found miR-30a-5p is highly expressed in the heart and is reduced in infarcted hearts. Further evidence showed that miR-30a-5p acts as a protective molecule to maintain myocardial remodeling, fibrosis, and mitochondrial structure. Mitochondrial function, ATP production, and mitochondrial respiratory chain proteins were positively regulated by miR-30a-5p. Mechanistically, alterations in these properties depend on SIRT1, which modulates miR-30a-5p-regulated mitochondrial metabolism. Remarkably, reactivation of SIRT1 prevented miR-30a-5p deficiency-aggravated myocardial infarction-induced myocardial remodeling. These data identified miR-30a-5p as a critical modulator of mitochondrial function in cardiomyocytes and revealed that the miR-30a-5p-SIRT1-mitochondria network is essential for myocardial infarction-induced cardiac remodeling.