Beneficial effects of metformin on primary cardiomyocytes via activation of adenosine monophosphate-activated protein kinase

• Published in: Chinese medical journal 2011-06, Vol.124 (12), p.1876-1884
• Main Authors: Wang, Xiao-Fang, Zhang, Jin-Ying, Li, Ling, Zhao, Xiao-Yan
• Format: Article
• Language: English
• Subjects: Aminoimidazole Carboxamide - analogs & derivatives; Aminoimidazole Carboxamide - pharmacology; AMP-Activated Protein Kinases - physiology; Animals; Apoptosis - drug effects; Cell Survival - drug effects; Cells, Cultured; Hypoglycemic Agents - pharmacology; Metformin - pharmacology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - metabolism; Nitric Oxide Synthase Type III - genetics; Rats; Rats, Wistar; Ribonucleotides - pharmacology; RNA, Messenger - analysis; Transforming Growth Factor beta1 - genetics; Tumor Necrosis Factor-alpha - genetics; 二甲双胍; 心肌细胞培养; 有益作用; 激活; 碱性成纤维细胞生长因子; 磷酸活化; 腺苷; 蛋白激酶
• ISSN: 0366-6999; 2542-5641
• DOI: 10.3760/cma.j.issn.0366-6999.2011.12.020

Background Metformin has become a cornerstone in the treatment of patients with type-2 diabetes. Accumulated evidence suggests that metformin supports direct cardiovascular effects. The present study aimed to investigate if metformin has beneficial effects on primary cardiomyocytes damaged by H2O2, and reveal the potential mechanism of action of metformin. Methods Cardiomyocytes were incubated in the presence of 100μmol/L H2O2 for 12 hours. Cardiomyocytes were pretreated with metformin at different concentrations and time and with aminoimidazole carboxamide ribonucleotide （AICAR） （500μmol/L）, an adenosine monophophate （AMP）-activated protein kinase （AMPK） agonist for 60 minutes before the addition of H2O2. Other cells were preincubated with compound C （an AMPK antagonist, 20μmol/L） for 4 hours. The viability and apoptosis of cells were analyzed. AMPK, endothelial nitric oxide synthase （eNOS）, and transforming growth factor （TGF）-β1 were analyzed using immunblotting. Results Metformin had antagonistic effects on the influences of H2O2 on cell viability and attenuated oxidative stress-induced apoptosis. Metformin also increased phosphorylation of AMPK and eNOS, and reduced the expression of TGF-β1, basic fibroblast growth factor （bFGF）, and tumor necrosis factor （TNF）-α. Conclusions Metformin has beneficial effects on cardiomyocytes, and this effect involves activation of the AMPK-eNOS pathway. Metformin may be potentially beneficial for the treatment of heart disease.