Regulation Of IRE1? On The Process Of Re-endothelialization After Vascular Injury

A low level of endoplasmic reticulum stress can protect cells by inducing unfolded protein response.However,pathological and chronic endoplasmic reticulum stress often leads to tissue dysfunction and causes many disease,such as neurodegenerative disorders,inflammatory disease,cancer and cardiovascular disease.It has been reported that cardiovascular diseases are the main diseases endangering human health nowadays.More and more studies show that endoplasmic reticulum stress is an important event in the occurrence,development and clinical progress of cardiovascular diseases.IRE1? is an important endoplasmic reticulum stress sensor.IRE1 has both kinase activity and endonuclease activity.It has also become clear that IRE1? can monitor cellular homeostasis beyond endoplasmic reticulum stress.This study focused on the regulation mechanism of IRE1? in endothelial cells in the process of re-endothelialization after vascular injury.Firstly,we constructed IRE1?-specific knockout mice,then performed femoral artery injury and carotid artery surgery in mice,and observed the degree of intimal neogenesis after surgery.HE stain showed that the knockout of IRE1? could promote the proliferation of smooth muscle cells induced by endothelial injury,and aggravate vascular restenosis.Evans blue staining and aortic ring test showed that the absence of IRE1? in endothelial cells reduced the degree of re-endothelialization.Subsequently,in vitro,we used siRNA to knock down the expression of IRE1? in HUVEC cells to study the regulation mechanism of IRE1? on endothelial cells.The results showed that the deletion of IRE1? inhibited the proliferation of endothelial cells and caused cell cycle arrest.Transwell and tube formation showed that the deletion of IRE1? also inhibited the migration and angiogenesis of endothelial cells.Through the above studies,we found that the regulation mechanism of IRE1? in endothelial cells in the process of re-endothelialization.The knockout of IRE1? can inhibit the proliferation,migration and angiogenesis of endothelial cells,and then reduce the degree of re-endothelialization after endothelial injury,thereby causing endothelial neogenesis and aggravating the rate of vascular restenosis.Previously,the important effects of endoplasmic reticulum stress on vascular function were mainly concentrated on vascular smooth muscle.In this In this research,the function of IRE1? in endothelium is briefly described for the first time.As a receptor of endoplasmic reticulum stress,IRE1? can directly regulate the proliferation and migration of endothelial cells,which will directly affect the process of reendothelialization after vascular repair.