Metformin attenuates angiotensin II‑induced cardiomyocyte hypertrophy by upregulating the MuRF1 and MAFbx pathway

Du,Fawang; Cao,Yalin; Ran,Yan; Wu,Qiang; Chen,Baolin

doi:10.3892/etm.2021.10665

Metformin attenuates angiotensin II‑induced cardiomyocyte hypertrophy by upregulating the MuRF1 and MAFbx pathway

Authors:
- Fawang Du
- Yalin Cao
- Yan Ran
- Qiang Wu
- Baolin Chen
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Affiliations: Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China, Department of Nephrology, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550002, P.R. China
Published online on: August 31, 2021 https://doi.org/10.3892/etm.2021.10665
Article Number: 1231
Copyright: © Du et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Pathological cardiac hypertrophy induced by aging and neurohumoral activation, such as angiotensin II (Ang II) activation, is an independent risk factor for heart failure. The muscle really interesting new gene‑finger protein‑1 (MuRF1) and muscle atrophy F‑box (MAFbx) pathway has been previously reported to be an important mechanism underlying the pathogenesis of cardiac hypertrophy. Metformin is currently the first‑line blood glucose‑lowering agent that can be useful for the treatment of cardiovascular diseases. However, the potential role of metformin in the modulation of MuRF1 and MAFbx in cardiomyocyte hypertrophy remains poorly understood. The present study used H9c2 cells, a cardiomyocyte cell model. The surface area of cultured rat H9c2 myoblasts was measured and the expression levels of MuRF1 and MAFbx were quantified using western blot or reverse transcription‑quantitative PCR. H9c2 cells were transfected with MuRF1 and MAFbx small interfering (si) RNA. The present study revealed that Ang II treatment significantly increased the cell surface area of model cardiomyocytes. Additionally, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) mRNA and protein expression was increased following this treatment. Ang II also downregulated MuRF1 and MAFbx protein and mRNA expression. In the H9C2, treatment with metformin attenuated hypertrophic remodeling. In addition, expression of ANP and BNP was significantly reduced in metformin‑treated H9C2 cells. The results indicated that metformin increased the activity of MuRF1 and MAFbx and upregulated their expression, the knockdown of which resulted in deteriorative Ang II‑induced cell hypertrophy, even following treatment with metformin. Taken together, data from the present study suggest that metformin can prevent cardiac hypertrophy through the MuRF1 and MAFbx pathways.

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