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Microvasc Res. 2018 Sep;119:98-104. doi: 10.1016/j.mvr.2018.05.006. Epub 2018 May 17.

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

Author information

1
Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, Heilongjiang Province, China.
2
Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin, 150001, Heilongjiang Province, China; Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin, 150001, Heilongjiang Province, China. Electronic address: ly99ly@vip.163.com.

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 improved by ticagrelor. In vitro, the induction of ER stress and inhibited eNOS phosphorylation in REACs exposed to AngII as well as tunicamycin was reversed by co-culturing with ticagrelor. In conclusion, ticagrelor protects against AngII-induced endothelial dysfunction via alleviating ER stress.

KEYWORDS:

AngII; Endoplasmic reticulum stress; Endothelial dysfunction; Ticagrelor

PMID:
29777791
DOI:
10.1016/j.mvr.2018.05.006
[Indexed for MEDLINE]

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