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.
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: Joao Incio; Jennifer A Ligibel; Daniel T McManus; Priya Suboj; Keehoon Jung; Kosuke Kawaguchi; Matthias Pinter; Suboj Babykutty; Shan M Chin; Trupti D Vardam; Yuhui Huang; Nuh N Rahbari; Sylvie Roberge; Dannie Wang; Igor L Gomes-Santos; Stefan B Puchner; Christopher L Schlett; Udo Hoffmman; Marek Ancukiewicz; Sara M Tolaney; Ian E Krop; Dan G Duda; Yves Boucher; Dai Fukumura; Rakesh K Jain Journal: Sci Transl Med Date: 2018-03-14 Impact factor: 17.956
Authors: Belén Picatoste; Elisa Ramírez; Alicia Caro-Vadillo; Cristian Iborra; Sara Ares-Carrasco; Jesús Egido; José Tuñón; Oscar Lorenzo Journal: PLoS One Date: 2013-10-21 Impact factor: 3.240