IMPACT OF METFORMIN ON THE EXPRESSION OF α- AND β-MHC GENES AFTER MYOCARDIAL INFARCTION IN MICE
DOI:
https://doi.org/10.11603/2415-8798.2019.2.10026Keywords:
metformin, ischemia/reperfusion, myocardial remodeling, hypertrophy, α-MHC, β-MHCAbstract
Type 2 diabetes is diagnosed in more than 65 % of patients who die as the result of cardiovascular disease. Metformin is a drug of choice for the treatment of type 2 diabetes which exerts cardioprotective effects. However, the molecular mechanisms of cardiomyocyte protection remain unclear and require further study. Hypertrophy of cardiomyocytes plays a leading role in the development of heart failure and is considered to be the result of imbalance between prohypertrophic and antihypertrophic factors and their mechanisms which control cell growth. In case of heart failure and hypertrophy, dysfunction of α-MHC and β-MHC genes occurs. Normally, α-MHC is a dominant isoform, however, when cardiac dysfunction occurs, the β-MHC gene is upregulated.
The aim of the study – to investigate the effects of metformin on hypertrophy of cardiomyocytes and the expression of α-MHC and β-MHC genes after myocardial infarction in mice.
Materials and Methods. C57BI/6J type mice were exposed to ischemia/reperfusion injury. To assess the translational potential of metformin study was designed to determine whether treatment with metformin in a dose of 5 mg/kg/day, initiated 15 minutes after the onset of reperfusion and maintained for 14 days induced cardioprotection in mice subjected to cardiac I/R. Cardiac sections were stained with hematoxylin and eosin. The evaluation of cardiac structural alterations was performed using ImageJ software. α-MHC and β-MHC expression levels were measured using quantitative RT-PCR analysis.
Results and Discussion. Ischemia/reperfusion injury caused hypertrophy of the cardiomyocytes. Histological analyses of cardiac sections stained with hematoxylin and eosin demonstrated a significant decrease in myocyte hypertrophy in metformin-treated mice as compared with vehicle-treated mice. In addition, ischemia/reperfusion induced β-MHC upregulation, although there was no significant change in α-MHC expression. It was found that metformin has no effect on the expression of α- and β-MHC genes.
Conclusions. Metformin protects cardiomyocytes from hypertrophic remodeling after myocardial infarction in mice. This cardioprotective effect is provided independently of α- and β-MHC pathways.
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