Mitoquinone Prevents Cardiac Dysfunction by Normalizing Mitochondrial ROS and Calcium Handling in Acute Myocardial Infarction

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Abstract
Acute myocardial infarction (MI) is the leading cause of heart failure (HF). However, the role of mitochondrial ROS (ROSm) in early MI dysfunction remains unclear. This study aimed to evaluate the impact of MitoQ on cardiac function in cases of heart HF following MI. Male Wistar rats were divided into four experimental groups: Sham, Infarct, Sham+MitoQ, and Infarct+MitoQ. MitoQ was administered orally (8 mg/kg/dia) for 7 days. Hemodynamic parameters, infarct area, papillary muscle contractility, cardiomyocyte mechanics, Ca 2+ transients, and total and mitochondrial superoxide (DHE and MitoSOX) were assessed. After 7 days of MI, rats exhibited impaired contractility, altered inotropic response to extracellular Ca 2+ , cardiomyocyte hypertrophy, and increased total and ROSm. MitoQ prevented body weight loss and significantly improved hemodynamic parameters compared to the Infarct group. In papillary muscles, MitoQ restored basal isometric force and the inotropic response to extracellular Ca 2+ . In cardiomyocytes, it attenuated hypertrophy, preserved shortening, and reduced ([Ca 2+ ]i) transient amplitude. MitoQ significantly decreased total and mitochondrial O 2 • − production. It selectively reduced NOX1 expression under simulated conditions but did not significantly affect NOX2, SOD1, or catalase expression in the context of MI. MitoQ prevented contractile dysfunction, suggesting that mitochondrial oxidative stress plays a decisive role in myocardial dysfunction during the acute phase of MI. Targeting antioxidant therapy to the mitochondria represents a promising strategy for preventing post‐infarction heart failure and opens new perspectives for the development of more effective interventions in the treatment of cardiovascular diseases.
Funding Information
  • Fundação de Amparo à Pesquisa e Inovação do Espírito Santo (TO2022‐6C3F7)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (151271/2024‐0)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (442473/2023‐0)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (407654/2025‐9)
  • Conselho Nacional de Desenvolvimento Científico e Tecnológico (444251/2024‐3)
  • Fundação de Amparo à Pesquisa do Estado de Minas Gerais (APQ‐04203‐23)
  • Fundação de Amparo à Pesquisa do Estado de Minas Gerais (APQ‐02501‐25)
  • Fundação de Amparo à Pesquisa do Estado de Minas Gerais (APQ‐04900‐22)

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