Resveratrol protects against myocardial ischemic injury in obese mice via activating SIRT3/FOXO3a signaling pathway and restoring redox homeostasis

作者：Xi Zhu, En Ma, Yixuan Ge, Yuan Meng, Xiaowei Guo, Jun Peng, Weidong Zhu, Dan‐ni Ren, Da Wo · 发表于：Biomedicine & Pharmacotherapy · 年份：2024 · DOI：10.1016/j.biopha.2024.116476 · 被引用次数：24 · 研究领域：Sirtuins and Resveratrol in Medicine、FOXO transcription factor regulation、Cardiac Fibrosis and Remodeling

BACKGROUND: Increasing global overweight and obesity rates not only increase the prevalence of myocardial infarction (MI), but also exacerbate ischemic injury and result in worsened prognosis. Currently, there are no drugs that can reverse myocardial damage once MI has occurred, therefore discovering drugs that can potentially limit the extent of ischemic damage to the myocardium is critical. Resveratrol is a polyphenol known for its antioxidant properties, however whether prolonged daily intake of resveratrol during obesity can protect against MI-induced damage remains unexplored. METHODS: We established murine models of obesity via high-fat/high-fructose diet, along with daily administrations of resveratrol or vehicle, then performed surgical MI to examine the effects and mechanisms of resveratrol in protecting against myocardial ischemic injury. RESULTS: Daily administration of resveratrol in obese mice robustly protected against myocardial ischemic injury and improved post-MI cardiac function. Resveratrol strongly inhibited oxidative and DNA damage via activating SIRT3/FOXO3a-dependent antioxidant enzymes following MI, which were completely prevented upon administration of 3-TYP, a selective SIRT3 inhibitor. Hence, the cardioprotective effects of prolonged resveratrol intake in protecting obese mice against myocardial ischemic injury was due to reestablishment of intracellular redox homeostasis through activation of SIRT3/FOXO3a signaling pathway. CONCLUSION: Our findings...