Myocardial Ischemia-Reperfusion Injury: Therapeutics from a Mitochondria-Centric Perspective

Abstract

Coronary arterial disease is the most common cardiovascular disease. Myocardial ischemia-reperfusion injury caused by the initial interruption of organ blood flow and subsequent restoration of organ blood flow is an important clinical problem with various cardiac reperfusion strategies after acute myocardial infarction. Even though blood flow recovery is necessary for oxygen and nutrient supply, reperfusion causes pathological sequelae that lead to the aggravation of ischemic injury. At present, although it is known that injury will occur after reperfusion, clinical treatment always focuses on immediate recanalization. Mitochondrial fusion, fission, biogenesis, autophagy, and their intricate interaction constitute an effective mitochondrial quality control system. The mitochondrial quality control system plays an important role in maintaining cell homeostasis and cell survival. The removal of damaged, aging, and dysfunctional mitochondria is mediated by mitochondrial autophagy. With the help of appro-priate changes in mitochondrial dynamics, new mitochondria are produced through mitochondrial biogenesis to meet the energy needs of cells. Mitochondrial dysfunction and the resulting oxidative stress have been associated with the pathogenesis of ischemia/reperfusion (I/R) injury, which play a crucial role in the pathophysiological process of myocardial injury. This review aimed at elucidating the mitochondrial quality control system and establishing the possibility of using mitochondria as a potential therapeutic target in the treatment of I/R injuries.

A Selective Inhibitor of Cardiac Troponin I Phosphorylation by Delta Protein Kinase C (δPKC) as a Treatment for Ischemia-Reperfusion Injury

“…Mitochondrial dysfunction is a key feature of IR injury [ 16 , 17 , 18 , 19 , 20 , 21 , 22 ], and the pan-inhibition of δPKC, with δV1-1, prevents IR-induced increases in mitochondrial oxidant production, and decreases in ATP levels [ 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. However, the mechanism by which δPKC causes mitochondrial dysfunction, and the protein substrate that mediates it, have not been identified.…”

“…An IR event leads to critical changes in mitochondrial function, bioenergetics, and redox balance in the cardiomyocyte [ 18 , 37 ]. These mitochondrial changes result in cell death, tissue remodeling, and contractile dysfunction [ 21 ]. Here, we measured the rates of oxygen consumption and production of the oxidant species H 2 O 2 from isolated cardiac mitochondria after IR.…”

HJ11 decoction restrains development of myocardial ischemia-reperfusion injury in rats by suppressing ACSL4-mediated ferroptosis

“…These findings imply that HJ11 decoction alleviated myocardial I/R injury by suppressing ACSL4-mediated ferroptosis. It is well known that apoptosis and ferroptosis are two different forms of cell death ( Zhou et al, 2021 ). This study revealed that HJ11 decoction attenuated apoptosis and ferroptosis in the myocardial tissues of myocardial I/R injury rats.…”

Yin and Yang of NADPH Oxidases in Myocardial Ischemia-Reperfusion

“…There are several sources of ROS during myocardial I/R injury, including the mitochondrial electron transport chain (ETC) [ 9 , 10 , 11 ], xanthine oxidase [ 12 , 13 ], and Noxs [ 2 , 14 , 15 ]. Of these, Noxs are major contributors to ROS production during myocardial I/R injury [ 16 ].…”