Study On The Mechanism Of Exosomes Derived From Hypoxia Induced MSCs In Promoting Angiogenesis

Preface:Myocardial infarction,as a serious complication of coronary heart disease,is one of the major cardiovascular diseases that endanger human health.In recent years,Mesenchymal Stem Cells(MSCs)for the treatment of myocardial infarction has attracted more attention,especially its paracrine effect,being considered as the major mechanism of its protective role in MI.Several studies have shown that exosomes secreted by MSCs can promote myocardial repair and angiogenesis after MI.Cytokines and miRNAs contained in exosomes are the main performers of their biological effects.Hypoxia preconditioning can enhance the function of MSCs derived exosomes in promoting angiogenesis,but the specific mechanism remains to be further studied and elaborated.Methods:MSCs were cultured in hypoxic and normoxic environments and their exosomes were isolated respectively.The expression of miR-214 in MSCs and exosomes was detected by qPCR.The capacity of HUVECs in cell migration and tubular formation was detected after co-cultured with different exosomes.The interaction between miR-214 and ATM gene was verified by the double-luciferase assay.The expression of ATM gene in HUVECs was detected by Western Blot.Results:The expression level of miR-214 in MSCs and exosomes after hypoxia induced was significantly upregulated.In addition,exosomes of the hypoxia preconditioning group played a better role in promoting the migration and tube formation of HUVECs.According to loss/gain of function strategy,we verified that miR-214 promoting angiogenesis by inhibiting ATM expression.Conclusions:Hypoxic environment can induce the increased expression of miR-214 in MSCs derived exosomes,thereby suppressing the expression of ATM gene and then promote angiogenesis.