High shear stress-induced pulmonary hypertension alleviated by endothelial progenitor cells independent of autophagy

Background:Pulmonary hypertension(PH)is a progressive disease characterized by lung endothelial cell dysfunction and Vascular remodeling.Endothelial progenitor cells(EPCs)have been proved to be a potential therapeutic strategy to treat PH.Autophagy has been found to be protective to hypoxia-induced PH.In this study,we applied high shear stress(HSS)-induced PH,and examined whether EPCs confer resistance against HSS-induced PH through autophagy.Methods:Pulmonary microvascular endothelial cells(PMVECs)were cultured under HSS with pro-inflammatory factors in an artificial capillary system to mimic the PH condition.Levels of p62,a selective autophagy substrate,were quantified by western blotting.Cell viability was determined by trypan blue exclusion test.Results:The p62 level in PMVECs was increased at 4 hours after HSS,peaked at 12 hours and declined at 24 hours.The cell viability gradually decreased.Compared with PMVECs cultured by empty medium,in cells cultured by EPC-conditioned medium(EPC-CM),the cell viability was significantly higher;however,p62 levels were also significantly higher,suggesting inhibition of autophagy by EPC-CM.Adding choloquine to suppress autophagy decreased the cell viability of PMVECs under PH.Conclusions:EPC-CM could suppress the autophagic activity of PMVECs in HSS-induced PH.However,suppression of autophagy leads to ceil death.EPCs could fight against PH through cellular or molecular pathways independent of autophagy.But it is not proved if induction of autophagy could be a potential strategy to treat HSS-induced PH as hypoxia-induced PH.