Overexpression of zinc‐finger protein 418 inhibits pathological cardiac remodelling after acute myocardial infarction

Abstract

AbstractAimsZinc‐finger protein 418 (ZNF418) has been confirmed to be expressed in myocardial tissue. However, the role and mechanism of ZNF418 in pathological myocardial remodelling after myocardial infarction (MI) have not been reported. This study was to elucidate the effect and mechanism of ZNF418 on ventricular remodelling after MI in mice.Methods and resultsMI mice and H9c2 cardiomyocytes were used to conduct in vivo and in vitro experiments, respectively. ZNF418 expression was regulated by adeno‐associated virus 9 and adenovirus vectors. Pathological analysis, echocardiography, and molecular analysis were performed. ZNF418 was down‐regulated in the left ventricular tissues of post‐MI mice. In contrast, ZNF418 overexpression decreased mortality and improved cardiac function in MI mice. The MI mice exhibited a significantly increased cross‐sectional area of myocardial cells and elevated protein expression levels of myocardial hypertrophy markers ANP, BNP, and β‐MHC (all P < 0.05). Moreover, a significantly increased area of myocardial fibrosis and protein expression levels of myocardial fibrosis markers collagen I, collagen III, and CTGF were observed in MI mice (all P < 0.05) in MI mice. All of the above negative effects in MI mice were ameliorated in ZNF418 overexpressed mice (all P < 0.05). Mechanistically, ZNF418 overexpression inhibited the activation of the MAPK signalling pathway, as evidenced by the in vivo and in vitro experiments.ConclusionsOverexpression of ZNF418 could improve cardiac function and inhibit pathological cardiac remodelling by inhibiting the MAPK signalling pathway in post‐MI mice.