GP6 promotes the development of cerebral ischemic stroke induced by atherosclerosis via the FYN-PKA-pPTK2/FAK1 signaling pathway

Abstract

Background. Cerebrovascular disease is currently a serious threat to human health and life, commonly including cerebral infarction, cerebral hemorrhage and transient cerebral ischemia, among others. Objectives. To explore the role and e molecular mechanism of GP6 in the development of cerebral ischemic stroke (CIS) induced by atherosclerosis (AS). Materials and methods. Forty-five male New Zealand white rabbits were randomly divided into 3 groups: the control, CIS model and anti-GP6 group. Carotid artery tissues and blood of the white rabbits were collected for analysis. Hematoxylin and eosin (H&E) staining was used to analyze the pathological characteristics of vascular endothelial injury. Flow cytometry (FCM) was performed to analyze the content of Th1 and Th17 in blood. Immunohistochemistry was used to analyze the distribution and relative expression of FCER1G, ITGA2 and GP6 proteins in the carotid artery and cerebrovascular tissues. Western blot was applied to determine the protein expression of GP6, FYN, PKA, pPTK2, and pFAK1 in carotid artery tissues of the rabbits. Results. In the CIS model group, there was lymphocyte infiltration, fibrous tissue formation, and the formation of thrombus and lipid plaques. In the anti-GP6 group, scattered thin plaques were observed, and no obvious foam cell deposition was observed. The Th1 and Th17 content was significantly decreased in the CIS model group compared to the control and anti-GP6 group. The relative expression of FCER1G, ITGA2 and GP6 in the CIS model group was significantly higher compared to those in the control group and anti-GP6 group. The protein expression of GP6, FYN, PKA, pPTK2, and pFAK1 in the CIS model group were markedly higher compared to those in the control group and anti-GP6 group. Conclusions. GP6 can promote the development of CIS by activating the FYN-PKA-pPTK2/FAK1 signaling pathway.