Metformin Increases Cardiac Rupture After Myocardial Infarction via the AMPK-MTOR/PGC-1α Signaling Pathway in Rats with Acute Myocardial Infarction.

Content Provider	Europe PMC
Author	Hua, Jinghai Liu, Zhanghua Liu, Zuheng An, Dongqi Lai, Wenyan Zhan, Qiong Zeng, Qingchun Ren, Hao Xu, Dingli
Copyright Year	2018
Abstract	BackgroundCardiac rupture often occurs after acute myocardial infarction due to complex and unclear pathogenesis. This study investigated whether metformin increases the incidence of cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1α signaling pathway.Material/MethodsAn acute myocardial infarction (MI) mouse model was established. A series of experiments involving RT-qPCR, Western blot, TUNEL staining, and Masson staining were performed in this study.ResultsMyocardial infarction occurred, resulting in the cardiac rupture, and the expression level of PGC-1α increased in the cardiac myocardium. Meanwhile, the proportion of myocardial NT-PGC-1α/PGC-1α decreased. The expression level of myocardial PGC-1α in MI mice with cardiac rupture after MI was significantly higher than that in the mice without cardiac rupture, and the ratio of myocardial NT-PGC-1α/PGC-1α was low. In addition, increasing the dose of metformin significantly increased the incidence of cardiac rupture after myocardial infarction in MI mice. High-dose metformin caused cardiac rupture in MI mice. Moreover, high-dose metformin (Met 2.0 nM) reduces the proportion of NT-PGC-1α/PGC-1α in primary cardiomyocytes of SD mice (SD-NRVCs [Neonatal rat ventricular cardiomyocytes]), and its effect was inhibited by Compound C (AMPK inhibitor). Further, after 3 days of treatment with high-dose metformin in MI mice, myocardial fibrin synthesis decreased and fibrosis was significantly inhibited. Meanwhile, cardiomyocyte apoptosis increased significantly. With the increase in metformin concentration, the expression level of myocardial LC3b gradually increased in MI mice, suggesting that metformin enhances the autophagy of cardiomyocytes.ConclusionsThese results suggest that metformin increases cardiac rupture after myocardial infarction through the AMPK-MTOR/PGC-1α signaling pathway.
ISSN	12341010
Journal	Medical Science Monitor : International Medical Journal of Experimental and Clinical Research
Volume Number	24
PubMed Central reference number	PMC6180847
PubMed reference number	30275441
e-ISSN	16433750
DOI	10.12659/msm.910930
Language	English
Publisher	International Scientific Literature, Inc.
Publisher Date	2018-10-02
Access Restriction	Open
Rights License	This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) © Med Sci Monit, 2018
Subject Keyword	Heart Rupture Metformin Myocardial Infarction
Content Type	Text
Resource Type	Article
Subject	Medicine