MitoQ attenuates cardiomyocyte hypertrophy and collagen deposition in post-myocardial infarction remodelling

Abstract Introduction After acute myocardial infarction (MI), the cardiac ventricle undergoes morphological, structural, and functional changes, a process known as cardiac remodelling (CR), influenced by metabolic dysfunction, oxidative stress (OS), and inflammation. Mitochondria, as major reactive oxygen species (ROS) sources, are potential therapeutic targets. However, conventional antioxidants struggle to reach mitochondria directly. In this context, mitochondrial-targeted antioxidants like mitoquinol mesylate (MitoQ) emerge as promising alternatives. Purpose To evaluate the impact of MitoQ treatment on CR following experimental acute MI in rats. Methods 120 male Wistar rats underwent acute MI via left coronary artery ligation or sham surgery and were divided into four groups: MI, MI+MitoQ, Sham, and Sham+MitoQ. Controls received tap water, while treated groups received MitoQ solution (500 µM) for three months; all had standard chow. After treatment, echocardiography and isolated heart tests were performed. The left ventricle was used for histological and biochemical analyses (OS markers, antioxidant enzymes, energy metabolism, metalloproteinase (MMP) activity, and protein expression by Western blot). Serum metabolomics was assessed via liquid chromatography-mass spectrometry, and gut microbiota composition was analyzed from fecal samples using 16S rRNA sequencing. Data were expressed as mean ± standard deviation, analyzed by Generalized Linear Model (gamma distribution), p0.05. Results The average infarct size was 50% ± 10% in MI and 53% ± 9% in MI+MitoQ. No differences were observed in food or water intake, body weight, energy metabolism enzymes, or gut microbiota. MI induced structural and functional changes in the left ventricle, confirmed by echocardiography and isolated heart studies. It also increased NFκB, pNFκB, Nrf2, SIRT1, collagen I, INF-γ, TNFα expression, and MMP-2, superoxide dismutase, and catalase activity in cardiac tissue, with no significant effect of MitoQ. In serum metabolomics, three metabolites were significantly altered between infarcted groups: 3,5-Di-tert-butyl-2-hydroxybenzaldehyde was increased in MI+MitoQ, while Creatinine and 2-Hydroxy-3,4-dihydro-2H-1,4-benzoxazin-3-one were decreased. The myocyte cross-sectional area was greater in infarcted animals, and it was reduced by 19% by MitoQ treatment MI: 302 ± 52 µm² vs MI+MitoQ: 244 ± 37 µm². Similarly, regarding interstitial collagen content, infarcted animals treated with MitoQ exhibited a relative reduction of 39% compared to the untreated group MI: 7.4 ± 2.7% vs MI+MitoQ: 4.7 ± 1.2%. Conclusion Although MitoQ did not affect functional or biochemical markers, it attenuated CR by reducing cardiomyocyte hypertrophy and interstitial collagen and induced changes in serum metabolomics.Left ventricle histological evaluation