Oxidative stress and mTOR signaling crucially regulate cardiometabolism in diabetic myocardial ischemia/reperfusion injury, highlighting metformin, Sirt1, and CTRP9 as potential therapeutic targets.
Oxidative stress and mTOR signaling are key pathophysiological mechanisms in diabetic myocardial ischemia/reperfusion injury, highlighting potential cardiometabolic targeted therapies.
Diabetes mellitus (DM) displays a high morbidity. The diabetic heart is susceptible to myocardial ischemia/reperfusion (MI/R) injury. Impaired activation of prosurvival pathways, endoplasmic reticulum (ER) stress, increased basal oxidative state, and decreased antioxidant defense and autophagy may render diabetic hearts more vulnerable to MI/R injury. Oxidative stress and mTOR signaling crucially regulate cardiometabolism, affecting MI/R injury under diabetes. Producing reactive oxygen species (ROS) and reactive nitrogen species (RNS), uncoupling nitric oxide synthase (NOS), and disturbing the mitochondrial quality control may be three major mechanisms of oxidative stress. mTOR signaling presents both cardioprotective and cardiotoxic effects on the diabetic heart, which interplays with oxidative stress directly or indirectly. Antihyperglycemic agent metformin and newly found free radicals scavengers, Sirt1 and CTRP9, may serve as promising pharmacological therapeutic targets. In this review, we will focus on the role of oxidative stress and mTOR signaling in the pathophysiology of MI/R injury in diabetes and discuss potential mechanisms and their interactions in an effort to provide some evidence for cardiometabolic targeted therapies for ischemic heart disease (IHD).
Zhao et al. (2017) conducted a review in Myocardial Ischemia/Reperfusion Injury in Diabetes. mTOR signaling and oxidative stress modulators was evaluated. Oxidative stress and mTOR signaling crucially regulate cardiometabolism in diabetic myocardial ischemia/reperfusion injury, highlighting metformin, Sirt1, and CTRP9 as potential therapeutic targets.