The Roles Of Phenotypic Transformation Of Vascular Smooth Muscle Cells Regulated By AGEs-RAGE In The Thoracic Aortic Dissection In Neonatal Rats

Research Backgrounds and Objective:Thoracic arotic dissection(TAD)is one kind of severe disease in clinic vascular surgery,the patients maybe go to different department in hospital at first such as the emergence department,the cardiothoracic surgery or vascular surgery.At present,the main treatment methods include thoracic endovascular aortic repair(TEVAR)and traditional graft replacement surgery.the mortality and postoperative complication rates were still high.The pathogenesis is so much and complex,but they have common foundation: some changes happened to the aortic wall especially for the middle of the wall.The aortic wall has contractibility and elasticity.Vascular smooth muscle cells(VSMCs)play an important role in the maintenance of vascular homeostasis and repair of vascular injury.AGEs can be combined with a variety of human tissues or cells to destroy them.Interactions between AGEs and RAGE can activate a variety of signaling pathways related to cell proliferation and apoptosis,which is associated with the occurrence and development of diabetes,Alzheimer's disease,atherosclerosis and other diseases.This study aims to observe the expression of advanced glycation end productsu(AGEs)and its receptor(RAGE)and explore the roles of phenotypic transformation of vascular smooth muscle cells(VSMCs)regulated by AGEs in the thoracic aortic dissection(TAD)in neonatal rats.Methods:1.The thoracic aortic dissection in neonatal rat model was established.The expression levels of AGEs and RAGE in thoracic aortic dissection tissues were detected.2.VSMCs phenotype transformation model was established by recombinant platelet derived growth factor BB(PDGF-BB)stimulation and starvation culture methods.The expression of RAGE was silenced by siRNA to explore the roles of phenotypic transformation of VSMCs regulated by AGEs in the thoracic aortic dissection in neonatal rats.The expression changes of SM ?-actin and calponin were detected by western blotting method.The expression changes of AGEs and RAGE were detected by ELISA and RT-PCR methods.Results:The expression levels of AGEs and its receptor RAGE in thoracic aortic dissection were significantly higher than that in normal thoracic aorta(P<0.01).The expression of AGEs and RAGE were negatively correlated with that of SM ?-actin and calponin.The regulation of AGEs on phenotypic transformation of VSMCs was blocked after silencing RAGE.Conclusions:AGEs can promote the transformation of VSMCs from the contractile type to the synthetic type in the thoracic aortic dissection and aortic aneurysm tissue.