Abstract:

Objective The purpose of this study was to explore the mechanism of exosomal miR⁃939 in hypoxia⁃induced cardiomyocytes injury via regulating ADCY6. Methods Serum from patients with acute myocardial infarction（Acute myocardial infarction，AMI）was collected，then exosome（exo）were isolated form serum and normal cardiomyocytes and subsequently H9C2 cells were treated with cobalt dichloride （CoCl2） to establish hypoxic cardiomyocyte model. Subsequently H9C2 cells were co ⁃cultured with normal cardiomyocytes derived exo and the expression of miR⁃939 was detected. MTT，transwell assay and flow cytometry was used to detect cell viability，migration and apoptosis individually.Double luciferase report experiment was used to verify the targeting regulatory relations between miR⁃939 and ADCY6. Results The expression of miR⁃939 in serum of AMI patients， serum exo and hypoxia ⁃treated cardiomyocytes were decreased. Normal cardiomyocytes derived exo promoted the proliferation and migration of hypoxia ⁃treated H9C2 cells and inhibited cardiomyocytes apoptosis（all P < 0.05）. Knocking down of miR⁃939 in exo partially counteracted the protective effect of exo. ADCY6 was proved to be a target gene of miR⁃939，exo promoted proliferation and migration but inhibited apoptosis of cardiomyocytes，more obvious effect was observed when exo combined with miR⁃939（P < 0.05）. The effect of exo⁃miR⁃939 on hypoxic cardiomyocytes was partially offset by ADCY6（all P < 0.05）. Conclusion Normal cardiomyocytes derivedexo inhibited the expression of ADCY6 by transfering miR ⁃939 to hypoxia ⁃treated cardiomyocytes，thereby reduced cardiomyocytes damage，the present research provided new molecular target in diagnosis and treatment of AMI.

Key words:

exosome, miR?939, ADCY6, acute myocardial infarction