title: Insights for Oxidative Stress and mTOR Signaling in Myocardial Ischemia/Reperfusion Injury under Diabetes.
abstract: 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).
authors.affiliation: Department of Cardiac Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Dajun
authors.initials: D
authors.lastname: Zhao
authors.affiliation: Department of Cardiac Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jian
authors.identifier: 0000-0003-2059-1912
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Xi'an Children's Hospital, Xi'an 710003, China.
authors.forename: Lifang
authors.identifier: 0000-0002-4004-9883
authors.initials: L
authors.lastname: Yang
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000737:chemistry; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000378:metabolism / Q000503:physiopathology*; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000737:chemistry; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D017202:Myocardial Ischemia / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D018384:Oxidative Stress; D011786:Quality Control; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species / Q000378:metabolism; D015427:Reperfusion Injury / Q000378:metabolism*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins
chemical_list: D052242:Adiponectin; D000975:Antioxidants; C543615:C1QTNF9B protein, human; D006023:Glycoproteins; D007004:Hypoglycemic Agents; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D019001:Nitric Oxide Synthase; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1