Ticagrelor protects against AngII-induced endothelial dysfunction by alleviating endoplasmic reticulum stress

Microvascular Research
Xiaoyu WangYue Li

Abstract

Ticagrelor has been reported to decrease cardiovascular mortality compared with clopidogrel. This benefit cannot be fully explained by the more efficient platelet inhibition. Many studies demonstrated that ticagrelor improved endothelial function, leaving the mechanism elusive though. The present study aims to investigate whether ticagrelor protects against endothelial dysfunction induced by angiotensinII (AngII) through alleviating endoplasmic reticulum (ER) stress. Male Sprague Dawley rats were infused with AngII or vehicle and administrated with ticagrelor or vehicle for 14 days. Reactive oxygen species (ROS) was detected. Aortas from normal mice were incubated with endoplasmic reticulum stress inducer tunicamycin with or without ticagrelor. Vasorecactivity was measured on wire myography. Rat aortic endothelial cells (RAECs) were pretreated with ticagrelor followed by AngII or tunicamycin. Endothelial nitric oxide synthase (eNOS) phosphorylation and ER stress markers were determined by western blotting. Impaired endothelial function, induction of ER stress, reduced eNOS phosphorylation and elevated ROS generation was restored by ticagrelor treatment in vivo. In addition, tunicamycin induced endothelial dysfunction was improv...Continue Reading

Citations

Jul 17, 2019·Journal of Cardiovascular Pharmacology·Song ZhangYue Li
Jun 28, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Min JiangRan Zhang
Dec 31, 2020·Drug Design, Development and Therapy·Hailu WuRuihua Shi

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