Inhibition of RBM25 preserves cardiac mitochondrial homeostasis and attenuates ischemic heart failure.

Heart failure (HF) after myocardial infarction (MI) is a serious complication that endangers the health of the patient. Mitochondrial dysfunction is an important mechanism in the development of ischemic HF. RNA-binding motif protein 25 (RBM25) is an RNA-binding protein that regulates a variety of biological processes and has been associated with HF. However, its role and underlying mechanism in mitochondrial dysfunction in ischemic HF remain unclear. Left anterior descending artery was ligated to establish an MI model in male C57BL/6 N mice, and cardiac function was evaluated by echocardiography and BNP levels at 4 weeks after ischemia. RBM25-overexpressing AC16 cell lines were constructed using a CRISPR-Cas9-mediated genome editing system. Adeno-associated virus 9-RBM25 shRNA was used to knock down RBM25 in mice. Mitochondrial morphology was observed by transmission electron microscopy, and protein expression was quantified by Western blotting. Cardiac pathology was evaluated by hematoxylin & eosin and Masson staining. Induction of post-ischemic HF in the MI model led to elevated RBM25 protein expression and impaired mitochondrial function in cardiomyocytes. Furthermore, overexpression of RBM25 in AC16 cells altered the expression of mitochondria-associated proteins. Notably, in vivo experiments showed that the knockdown of RBM25 could improve cardiac function after ischemia, along with maintaining mitochondrial morphology and the expression of mitochondrial-related proteins. These findings suggest that RBM25 could mediate HF progression post-infarction by impairing mitochondrial function. Thus, inhibition of RBM25 may have therapeutic potential in slowing down the progression of HF.