AUTHOR=Huang Kai-yu , Wang Jiao-ni , Zhou Ying-ying , Wu Shao-ze , Tao Lu-yuan , Peng Yang-pei , Que Jia-qun , Xue Yang-jing , Ji Kang-ting 

TITLE=Antithrombin III Alleviates Myocardial Ischemia/Reperfusion Injury by Inhibiting Excessive Autophagy in a Phosphoinositide 3-Kinase/Akt-Dependent Manner

JOURNAL=Frontiers in Pharmacology

VOLUME=Volume 10 - 2019

YEAR=2019

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2019.00516

DOI=10.3389/fphar.2019.00516

ISSN=1663-9812

ABSTRACT=Autophagy is fundamental to myocardial ischaemia/reperfusion (I/R) injury. While antithrombin III (AT) has been shown to protect cardiomyocytes against I/R injury, whether it modulates autophagy is unknown. The objective of this study was to investigate whether AT regulates autophagy during I/R injury and, if so, the potential mechanism involved. Our study showed that AT attenuated I/R injury both in vivo and in vitro. Autophagy was increased both in H9C2 myocytes and in mouse hearts following I/R injury. Stimulation of autophagy by rapamycin attenuated the protective effect of AT against H9C2 cell injury, suggesting that autophagy is important for the protective role of AT in I/R. Furthermore, the cardioprotective effects of AT were abolished by A6730, a specific Akt inhibitor. This study showed that AT exhibits a cardioprotective effect by modulating autophagy during I/R in a phosphoinositide 3-kinase/Akt-dependent manner.