Resveratrol, novel application by preconditioning to attenuate myocardial ischemia/reperfusion injury in mice through regulate AMPK pathway and autophagy level

Abstract

Myocardial ischemia/reperfusion injury (MI/RI) is the main cause of deaths in the worldwide, leading to severe cardiac dysfunction. Resveratrol (RSV) is a polyphenol plant‐derived compound. Our study aimed to elucidate the underlying molecular mechanism of preconditioning RSV in protecting against MI/RI. Mice were ligated and re‐perfused by the left anterior descending branch with or without RSV (30 mg/kg·ip) for 7 days. Firstly, we found that RSV pretreatment significantly alleviated myocardial infarct size, improved cardiac function and decreased oxidative stress. Furthermore, RSV activated p‐AMPK and SIRT1, ameliorated inflammation including the level of TNF‐α and IL‐1β, and promoting autophagy level. Moreover, neonatal rat ventricular myocytes (NRVMs) and H9c2 cells with knockdown the expression of AMPK, SIRT1 or FOXO1 were used to uncover the underlying molecular mechanism for the cardio‐protection of RSV. In NRVMs, RSV increased cellular viability, decreased LDH release and reduced oxidative stress. Importantly, Compound C(CpC) and EX527 reversed the effect of RSV against MI/RI in vivo and in vitro and counteracted the autophagy level induced by RSV. Together, our study indicated that RSV could alleviate oxidative stress in cardiomyocytes through activating AMPK/SIRT1‐FOXO1 signallingpathway and enhanced autophagy level, thus presenting high potential protection on MI/RI.

Effects of Resveratrol on Vascular Function in Retinal Ischemia-Reperfusion Injury

“…The substance was found in a variety of food sources, such as grapes, raspberries, mulberries, and peanuts [ 13 , 14 ]. Intriguingly, resveratrol was shown to exert tissue-protective properties in a variety of disease models, including studies that tested I/R effects in the heart, brain, spinal marrow, and kidney [ 15 , 16 , 17 , 18 , 19 , 20 ]. In the retina, resveratrol was shown to exert antiproliferative, antioxidant, anti-inflammatory, and anti-apoptotic effects [ 21 , 22 , 23 , 24 ].…”

Activation of moderate autophagy promotes survival of fat graft

“…Autophagy is a highly conserved cellular recycling process through which cellular components, including proteins, lipids, and organelles, are degraded in lysosomes and then recycled to maintain cellular homeostasis 13 . As demonstrated by current studies, moderate autophagy is beneficial to the survival of ischemic tissue 14–17 . During ischemia, suppressed oxidative phosphorylation of mitochondria leads to mitochondrial metabolic dysfunction, resulting in decreased adenosine triphosphate (ATP) production and increased harmful molecules including reactive excessive oxygen species (ROS), high levels of unfolded proteins and accumulative lactic acid produced by glycolysis 14–17 .…”

“…During ischemia, suppressed oxidative phosphorylation of mitochondria leads to mitochondrial metabolic dysfunction, resulting in decreased adenosine triphosphate (ATP) production and increased harmful molecules including reactive excessive oxygen species (ROS), high levels of unfolded proteins and accumulative lactic acid produced by glycolysis 14–17 . Once autophagy is activated, unnecessary or damaged organelles and proteins can be first encapsulated in autophagosomes and then transported to lysosomes for degradation 14–17 . Mitophagy refers to a special subtype of autophagy that leads to lysosomal degradation of dysfunctional mitochondria 18,19 .…”

“…It is generally believed that moderate autophagy is protective, while dysregulated autophagy has implications for health and disease 14,15,23 . However, the effect and mechanism of autophagy on fat graft survival have yet been reported.…”

“…[14][15][16][17] During ischemia, suppressed oxidative phosphorylation of mitochondria leads to mitochondrial metabolic dysfunction, resulting in decreased adenosine triphosphate (ATP) production and increased harmful molecules including reactive excessive oxygen species (ROS), high levels of unfolded proteins and accumulative lactic acid produced by glycolysis. [14][15][16][17] Once autophagy is activated, unnecessary or damaged organelles and proteins can be first encapsulated in autophagosomes and then transported to lysosomes for degradation. [14][15][16][17] Mitophagy refers to a special subtype of autophagy that leads to lysosomal degradation of dysfunctional mitochondria.…”