Abstract:

Objective The research aimed to investigate the role of miRNA⁃330⁃3p/Ap2m1 axis in theeffects of reduction of myocardial cell apoptosisand improvement of myocardial function in myocardial infarctionby GATA⁃4 overexpressed⁃mouse bone marrow mesenchymal stem cell（BMSC）⁃secreted exosomes（BMSC^GATA⁃4⁃exosome）. Method Mouse myocardial infarction models were established and then divided into seven groups. Eachmouse was injected with BMSC^miRNA⁃330⁃3p⁃mimic⁃exosome，BMSC^miRNA⁃330⁃3p⁃inhibitor⁃exosome，BMSC^GATA⁃4⁃exosome，BMSC^empty carrier⁃exosome，and BMSCexosome through the caudal vein for 48 hours. The untreated myocardial infarction group andnormal mice were included in the control group. Cardiac color ultrasound was used to detect cardiac function ineach group. The expression of miRNA⁃330⁃3p in myocardial infarction was detected by RT⁃PCR. Tunel assay wasused to detect the number of apoptotic cells in myocardial tissue of myocardial infarction in each group. Westernblot was used to detect the expression of the corresponding target gene Ap2m1 of miRNA⁃330⁃3p and Cnot4 protein.Results The BMSC^miRNA⁃673⁃5p⁃mimic⁃exosome group showed the most significant improvement in myocardial function inmyocardial infarction（P < 0.05）and the highest expression of miRNA⁃330⁃3p in cardiomyocytes（P < 0.05）. Thecardiomyocytes in the BMSC^miRNA⁃330⁃3p⁃mimic⁃exosome group had the lowest apoptosis rate（P < 0.05），and Ap2m1 inthe BMSC^miRNA⁃330⁃3p⁃mimic⁃exosome+myocardial cell culture group had the lowest expression（P < 0.05）. Conclusion Overexpressed GATA⁃4 bone marrow⁃derived mesenchymal stem cell exosomes inhibit the expression of Ap2m1protein against myocyte apoptosis through miRNA⁃330⁃3p.

Key words: miRNA?330?3p, Ap2m1 protein, GATA?4, exosome, mouse bone marrow?derived mesenchymal stem cells