title: Beneficial effects of metformin on primary cardiomyocytes via activation of adenosine monophosphate-activated protein kinase.
abstract: 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 100 µmol/L H2O2 for 12 hours. Cardiomyocytes were pretreated with metformin at different concentrations and time and with aminoimidazole carboxamide ribonucleotide (AICAR) (500 µmol/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, 20 µmol/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.
authors: Department of Cardiology, First Affiliated Hospital, College of Medicine, Zhengzhou University, Zhengzhou, Henan 450052, China.
authors: Xiao-Fang
authors: XF
authors: Wang
authors: Jin-Ying
authors: JY
authors: Zhang
authors: Ling
authors: L
authors: Li
authors: Xiao-Yan
authors: XY
authors: Zhao
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008687:Metformin / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000494:pharmacology; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D007004:Hypoglycemic Agents; D012333:RNA, Messenger; D012265:Ribonucleotides; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D000620:Aminoimidazole Carboxamide; D008687:Metformin; D052250:Nitric Oxide Synthase Type III; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide