Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury

Kai-yu Huang^1*, Jia-qun Que^1*, Ze-song Hu², Yong-wei Yu¹, Ying-ying Zhou³, Lei Wang², Yang-jing Xue¹, Kang-ting Ji^1✉, Xin-min Zhang^1✉

1. Department of Cardiology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
2. The Second School of Medicine, Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
3. Department of Endocrinology, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325027, Zhejiang, China.
*These authors contributed equally to this work.

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Citation:
Huang Ky, Que Jq, Hu Zs, Yu Yw, Zhou Yy, Wang L, Xue Yj, Ji Kt, Zhang Xm. Metformin suppresses inflammation and apoptosis of myocardiocytes by inhibiting autophagy in a model of ischemia-reperfusion injury. Int J Biol Sci 2020; 16(14):2559-2579. doi:10.7150/ijbs.40823. Available from http://www.ijbs.com/v16p2559.htm

Abstract

Metformin (Met) is a major widely used oral glucose lowering drug for the treatment of type 2 diabetes. It is reported that metformin could regulate autophagy in various diseases of cardiovascular system including in I/R injury, diabetic cardiomyopathy and heart failure. Autophagy plays a controversial role in ischemia/reperfusion (I/R) injury, and this research was performed to explore the cardioprotective effect of Met on I/R injury and discuss the underlying mechanism of autophagy in it. In vivo and in vitro, Met exerted cardioprotection function of decreasing myocardial inflammation and apoptosis with a decrease in the level of autophagy. Moreover, Met significantly inhibited autophagosome formation and restore the impairment of autophagosome processing, which lead to cardioprotection effect of Met. Akt was up-regulated in Met-treated I/R hearts and miransertib, a pan-AKT inhibitor, was able to reverse the alleviating autophagy effect of Met. We demonstrate that Met protects cardiomyocytes from I/R-induced apoptosis and inflammation through down regulation of autophagy mediated by Akt signaling pathway.

Keywords: Metformin, autophagy, apoptosis, inflammation, myocardial ischemia reperfusion