MAPK Phosphorylation Is Involved In The Vascular Endothelial Injury Under The Action Of Impinging Flow

Objective:Intracranial aneurysm is one of the common cerebrovascular diseases,which can cause intracranial hemorrhage,and seriously threaten the life and health of patients.It has been reported that the vascular endothelial function caused by complex hemodynamics is considered to be the initiating link of aneurysm formation.This study intends to construct a vascular endothelial cell injury model in vitro to explore the relevant mechanism of hemodynamics inducing endothelial cell inflammation.Method:A new T-cell hydrodynamic system designed by our research group was used to simulate the hemodynamic environment at the bifurcation of intracranial arteries,and the impinging flow of 500ml/min was applied to human umbilical vein endothelial cells(HUVEC)for 0,3,6 hours.The changes in cell morphology was observed,and the expression of MCP-1,ERK1/2,JNK,P38 and other related proteins in the cell were detected with Western Blot technology.Results:After the impinging flow,the cell density in region 1 and region 3 did not change significantly,and the vascular endothelial cell density in region 2 decreased significantly.As the impinging flow action time prolonged,the cell density in region2 showed a progressive decrease.At the same time,Western Blot found that the expression of MCP-1,c-jun,c-fos and the phosphorylation of JNK and P38 increased progressively.The expression of c-jun and MCP-1,c-fos and MCP-1decreased after treated with JNK specific inhibitor or P38 specific inhibitor respectively,but not with ERK1/2 specific inhibitor.Conclusion:Under the action of impinging flow,the cell density in the high wall shear stress(WSS)area is significantly reduced,and the JNK-c-jun/P38-c-fos pathway may regulate MCP-1 to participate in endothelial cell inflammation and promote intracranial aneurysms formation.