Mitofilin Mitigates Myocardial Damage in Acute Myocardial Infarction by Regulating Pyroptosis of Cardiomyocytes.

Acute myocardial infarction (AMI) can lead to sudden cardiac death after prolonged ischemia or heart failure (HF) and impaired left ventricular pump function. However, the underlying mechanism remains largely unknown. The purpose of this study was to investigate the role of mitofilin in alleviating AMI. Recombinant adenoviral vectors for mitofilin overexpression or mitofilin knockdown were constructed, respectively. A mouse AMI model was established and the effect of mitofilin on myocardial pyroptosis was examined by detecting the lactate dehydrogenase (LDH) level and inflammatory factors. Moreover, a cellular model of AMI was established by treating cardiomyocytes with hypoxia/reoxygenation (H/R). An enzyme-linked immunosorbent assay (ELISA) and a western blot analysis were used to detect the effect of mitofilin knockdown on the expression of pyroptosis-related factors. Furthermore, the regulatory role of mitofilin in PI3K/AKT pathway was evaluated by the western blot and PI3K inhibitor. Mitofilin was downregulated in the heart tissue of the AMI mice and H/R induced cardiomyocytes. The overexpression of mitofilin significantly alleviated AMI and reduced pyroptosis-related factors. Meanwhile, in cardiomyocytes, mitofilin knockdown aggravated cellular damages by promoting pyroptosis. Further analysis showed that the anti-pyroptotic effect of mitofilin was dependent on the activation of the PI3K/AKT signaling pathway. Our study suggests that mitofilin regulates pyroptosis through the PI3K/AKT signaling pathway in cardiomyocytes to ameliorate AMI, which may serve as a therapeutic strategy for the management of AMI. Copyright © 2022 Ma, Liang, Diao, Wang and He.

Citation

Min Ma, Shi-Chu Liang, Kai-Yue Diao, Qin Wang, Yong He. Mitofilin Mitigates Myocardial Damage in Acute Myocardial Infarction by Regulating Pyroptosis of Cardiomyocytes. Frontiers in cardiovascular medicine. 2022;9:823591

PMID: 35586659

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