Int J Med Sci 2020; 17(9):1196-1206. doi:10.7150/ijms.44604

Research Paper

Downregulation of P300/CBP-Associated Factor Attenuates Myocardial Ischemia-Reperfusion Injury Via Inhibiting Autophagy

Liqiang Qiu1,2,3, Changwu Xu1,2,3 ✉, Hao Xia1,2,3, Jing Chen1,2,3, Huafen Liu1, Hong Jiang1,2,3

1. Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China.
2. Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China.
3. Hubei Key Laboratory of Cardiology, Wuhan 430060, China.

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Citation:
Qiu L, Xu C, Xia H, Chen J, Liu H, Jiang H. Downregulation of P300/CBP-Associated Factor Attenuates Myocardial Ischemia-Reperfusion Injury Via Inhibiting Autophagy. Int J Med Sci 2020; 17(9):1196-1206. doi:10.7150/ijms.44604. Available from http://www.medsci.org/v17p1196.htm

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Abstract

Cardiomyocyte autophagy plays an important role in myocardial ischemia-reperfusion injury (MIRI). P300/CBP-associated factor (PCAF) was involved in the regulation of autophagy. However, the role of PCAF in MIRI is currently unknown. This study was to investigate whether downregulation of PCAF attenuate MIRI. The results showed that the expression of PCAF was significantly increased in MIRI in vivo and in vitro. Downregulation of PCAF not only inhibited autophagy and damage of H9c2 cells induced by hypoxia-reoxygenation, but also reduced autophagy and myocardial infarct size during myocardial ischemia-reperfusion in rats. In addition, downregulation of PCAF promoted activation of PI3K/Akt/mTOR signaling pathway in cardiomyocytes during hypoxia-reoxygenation. Wortmannin, a PI3K/Akt inhibitor, could abrogate the effects of downregulation of PCAF on cardiomyocytes autophagy. These results demonstrated that downregulation of PCAF alleviated MIRI by inhibiting cardiomyocyte autophagy through PI3K/Akt/mTOR signaling pathway. Thus, PCAF may be a potential target for prevention and treatment of MIRI.

Keywords: P300/CBP-associated factor, Myocardial ischemia-reperfusion injury, Autophagy, Signaling pathway, Wortmannin