Metformin significantly reduced cardiac hypertrophy and fibrosis post-MI in rats, without affecting infarct size or cardiac function, while lowering oxidative stress and altering gut microbiota.
Does metformin attenuate post-infarction cardiac remodeling in a rat model of myocardial infarction?
In a rat model of myocardial infarction, metformin attenuated cardiac remodeling, reduced oxidative stress, and modulated gut microbiota and metabolomics, suggesting pleiotropic cardioprotective effects.
Tasa de eventos absoluta: 0% vs 0%
Abstract Background After myocardial infarction (MI), the cardiac ventricle undergoes morphological, structural, and functional changes, collectively known as cardiac remodelling, influenced by factors such as metabolic dysfunction, oxidative stress, and inflammation. Metformin (MET) has been studied beyond its glycaemic effects, with growing evidence suggesting it may provide direct cardioprotection, possibly due to anti-inflammatory, antiproliferative, and antioxidant properties. Recent research has also highlighted the role of the gut microbiota. Purpose This study aimed to evaluate the effect of MET on cardiac remodelling following MI in rats. Methods 70 non-diabetic male Wistar rats (220-250 g) were subjected to open-chest myocardial infarction via left coronary artery ligation or sham surgery. After seven days, ensuring homogeneity of MI size via echocardiography, rats were divided into the following groups: Sham non-treated (Sham, n=20); Infarct non-treated (Inf, n=27); and Infarct treated with MET (Inf+MET, n=23). MET was administered in drinking water at a dose of 250 mg/kg/day for 12 weeks, with all rats receiving standard chow. At the study's conclusion, we performed echocardiography, followed by euthanasia, functional studies on isolated hearts, left ventricular (LV) histology, LV metabolic enzymatic activity, oxidative stress analysis by spectrophotometry, LV protein expression by Western blotting, serum metabolomics via liquid chromatography-mass spectrometry, and gut microbiota composition using 16S rRNA sequencing. Statistical analysis was performed using one-way ANOVA with Tukey’s post-test, or Kruskal-Wallis and Dunn’s test, with p0.05 considered significant. Results The Inf+MET group consumed less food and water than the Inf group, though no significant difference in body weight was observed. Histological analysis revealed no differences in infarct size between the Inf and Inf+MET groups (50±10% vs 51±8%, respectively). MI induced increased LV volumes, and cardiac dysfunction, but MET did not interfere with these variables. On the other hand, the Inf+MET group exhibited a significant reduction in both cardiac hypertrophy and fibrosis, as confirmed by smaller cardiomyocyte cross-sectional areas and lower collagen deposition compared to the Inf group. Additionally, the Inf+MET group showed less oxidative stress and lower hexokinase activity in myocardial tissue compared to the Inf group. MET also increased both alpha- and beta-diversity of the intestinal microbiota. Furthermore, MET reduced six metabolites (arginine, nicotinamide, tryptophan, carnitine, butyrylcarnitine, and hippuric acid) and increased two (azelaic acid and suberic acid). Conclusion Metformin mitigates MI-induced cardiac remodelling in rats, through modulation of oxidative stress, myocardial energy metabolism, and gut microbiota. These findings provide valuable insights into the cardioprotective effects of MET in the context of post-MI remodelling.General results Histology, gut microbiota, metabolomics
Queiróz et al. (Sat,) reported a other. Metformin significantly reduced cardiac hypertrophy and fibrosis post-MI in rats, without affecting infarct size or cardiac function, while lowering oxidative stress and altering gut microbiota.