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

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.

Microgravity-induced stress mechanisms in human stem cell-derived cardiomyocytes

“…To this end, we used IMR90-hiPSCs-derived CMs to identify here a microgravity-controlled axis causing a senescence-like phenotype leading to contractile dysfunctions in CMs. To get evidence that SMG may induce also atrophy of the CMs, we investigated the effects of SMG on the expression of three genes MurF1 , FOXO and SMAD3 that serve as markers for cardiomyocytes atrophy ( Du et al., 2021 ; Ni et al., 2006 ; Tsui et al., 2015 ; Xin et al., 2017 ). As indicated in Figure S4 the, expression of all three genes was significantly upregulated in comparison to c-CMs.…”

Evidence that tirzepatide protects against diabetes-related cardiac damages

“…Further support for the involvement of MuRF-1 in cardiac fibrosis came from treatment in H9C2 cell lines by metformin enhanced the activity of MuRF1 and demonstrated a reduction in hypertrophic remodeling [ 46 ].…”

Sesamin suppresses angiotensin‐II‐enhanced oxidative stress and hypertrophic markers in H9c2 cells

“…Persistent myocardial hypertrophy leads to myocardial remodeling and left ventricular dilatation, leading to cardiomyopathy, myocardial fibrosis disease, and ultimately heart failure. [3][4][5] In addition, a previous report suggested that myocardial hypertrophy is characterized by an increase in myocardial cell mass and size caused by the activation of hypertrophic markers.…”

“…Myocardial hypertrophy plays a vital role in the development of CVD, and myocardial hypertrophy is an adaptive response and compensatory phenomenon made by myocardial cells in response to stress after cardiac injury, intending to maintain cardiac output and normal cardiac function. Persistent myocardial hypertrophy leads to myocardial remodeling and left ventricular dilatation, leading to cardiomyopathy, myocardial fibrosis disease, and ultimately heart failure 3–5 . In addition, a previous report suggested that myocardial hypertrophy is characterized by an increase in myocardial cell mass and size caused by the activation of hypertrophic markers.…”