The Effect And Mechanism Of Integrin β3 On Pulmonary Arterial Hypertension

Objective: Pulmonary arterial hypertension(PAH)is defined as a group of diseases characterized by pathological remodeling of distal pulmonary arterioles.Current drugs are more likely to dilate the constricted pulmonary arteries than to significantly improve survival.Therefore,it is urgent to find novel therapeutic targets to improve the clinical treatment status of PAH.Methods: In this study,we focused on the role of integrin β3 in the pathogenesis of PAH.Real-time quantitative PCR,western blotting,cellular immunofluorescence and immunohistochemistry were performed to verify the expression and activation levels of integrin β3 in the development of PAH ex vivo and in vitro.The si RNA and inhibitors(cyclo(RGDf K))for integrin β3 were used to demonstrate the role of integrin β3 in PDGFinduced pulmonary arterial smooth muscle cells(PASMCs)proliferation.Sh RNA for integrin β3 and cyclo(RGDf K)were used to validate the role of integrin β3 in TGFβ1-induced endothelial-to-mesenchymal transition(End MT)of human umbilical vein endothelial cells(HUVECs).Finally,we explored the protective effect of cyclo(RGDf K)on PAH animal models.Results: The results showed that integrin β3 was significantly upregulated in PAH animal pulmonary arteries,TGFβ1-induced HUVECs and PDGF-induced PASMCs.Knockdown or inhibition of integrin β3 in PASMCs inhibited them proliferation.Knockdown or inhibition of integrin β3 in HUVECs inhibited End MT in HUVECs.Cyclo(RGDf K)could improve pulmonary artery remodeling in the development of PAH by inhibiting PASMCs proliferation and End MT.Conclusions: Integrin β3 is a therapeutic target for PAH,and its inhibitior cyclo(RGDf K)is a potential therapeutic agent for PAH.