PDGFBB Promotes The Progression Of Atherosclerosis By Regulating EndMT Via PDGFRβ

Background and objective:atherosclerosis（AS）is the common pathological basis of various cardiovascular and cerebrovascular diseases,including coronary heart disease and cerebral stroke.How to effectively control the size and stability of AS plaque is of great significance to avoid ischemia and necrosis of local heart and brain tissue caused by vascular obstruction.It has been reported that vascular Endothelial cells undergo End MT under the stimulation of long-term high blood flow shear force and high lipid,and the latter proliferates and migrates to AS plaques to promote the formation and development of AS.However,the mechanism of End MT endothelial cells entering plaques has not been reported.PDGFBB is a regulatory factor that stimulates the growth of tissue cells and promotes the proliferation and migration of End MT endothelial.Methods:（1）in order to evaluate the expression of pdgf-bb and PDGFR and their correlation with endothelial End MT,we constructed a mouse model of atherosclerosis（apo E-/-）and detected the formation of aortic atherosclerotic plaques by gross oil red staining after aortic tissue was isolated.Subsequently,HE staining was used to observe the distribution of cells and plaques in the cross section of blood vessels,and the expression and localization of PDGFBB,PDGFR,CD31 and asma were detected by immunohistochemistry and immunofluorescence.（2）to verify the role of pdgf-bb in regulating endothelial End MT through up-regulation and action of PDGFR,thp-1 cells were first induced to be macrophages in vitro,and then foam-like cells were further induced by ox-ldl.The expression levels of PDGFBB in culture medium and intracellular were detected by Elisa and western blot respectively.Then,TGF TGF was used in vitro to induce HAEC cells to undergo mesenchymal transformation,and PDGFBB and PDGFR inhibitor（imatinib and small interfering RNA）were combined for treatment.Subsequently,the expression of PDGFR was detected by western blot,the migration ability of cells was detected by scratch test,and the migration and invasion ability of cells were detected by transwell test.Results:in the mouse model of atherosclerosis(apo E^-/-),the expression level of serum PDGFBB was positively correlated with the severity of aortic plaque,and the expression levels of PDGFBB and PDGFRβwere increased with the interstitial transformation of endothelial cells.PDGFBB was mainly expressed in the nucleus,and PDGFRβwas mainly expressed in cytoplasm.In vitro,macrophages can secrete a large amount of PDGFBB after being induced by ox-LDL into foam cells.Endothelial mesenchymal transformation（i.e.,CD31 expression decreased and a SMA expression increased）was verified in TGFβ-induced HAEC.When PDGFBB was added to endothelial mesenchymal transformed cells,the increased expression of PDGFRβwas accompanied by increased cell migration and invasion.Conclusion:in the development of atherosclerosis,pdgf-bb regulates endothelial cell End MT through PDGFR to promote the progression of atherosclerosis,and inhibition of this target provides a new idea for delaying the occurrence and development of atherosclerosis.