Ang-1 inhibited endoplasmic reticulum stress and apoptosis of VECs in rats with aSAH induced CVS through regulated PI3K/Akt pathway

Abstract

Aims: To explore angiopoietin-1 (Ang-1) involved in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH) through effected on endoplasmic reticulum stress (ERS) and apoptosis of vascular endothelial cells (VECs). Background: CVS accounts for high morbidity and mortality of aSAH. Abnormal cellular physiological processes of VECs play a critical rale in aSAH induced CVS. In addition, Ang-1 involve in the regulation of vascular structure and function. Objective: To study the role of Ang-1 played in CVS and the underlying mechanism. Methods: Blood samples of 130 aSAH patients were collected from 2016 to 2020 in West China Hospital of Sichuan University. Two-hemorrhage rodent model was employed to structured aSAH-induced CVS rat model. And oxyHb was used to treat VECs to constructed CVS cell model in vitro. ELISA was used to measure the level of Ang-1. HE staining was used to assess basilar arteries of rat. CCK-8 was used to detect cell viability ability. Flow cytometry was used to test the cell apoptosis rate. Western blotting was used to determine the expression level of ERS marker and apoptosis-related proteins. Results: There was an abnormally low expression of Ang-1 in CVS patients and CVS rats; besides, oxyHb treatment decreased Ang-1 in VECs in a concentration-dependent manner. Ang-1 treatment led to the basilar artery wall thinner and lumen circumference larger in CVS rat; moreover, in oxyHb treated VECs, Ang-1 treatment inhibited ERS and apoptosis. In addition, the expression of p-PI3K and p-Akt in the CVS group decreased, while the expression of p53 in the CVS group increased. The expression of p-PI3K and p-Akt in 8 CVS rat have negative correlation with expression of Ang-1, but the correlation between p53 and Ang-1 was positive. Furthermore, the results suggested that Ang-1 suppressed ERS and apoptosis of VECs through regulated PI3K/Akt/p53 pathway. Conclusion: Elevated Ang-1 inhibited p53 mediated ERS and apoptosis of VECs by activated PI3K/Akt pathway, Ang-1 might be an attractive treatment strategy for CVS.