Role of Oxidative Stress in Cardiac Dysfunction and Subcellular Defects Due to Ischemia-Reperfusion Injury

Abstract

Ischemia-reperfusion (I/R) injury is well-known to be associated with impaired cardiac function, massive arrhythmias, marked alterations in cardiac metabolism and irreversible ultrastructural changes in the heart. Two major mechanisms namely oxidative stress and intracellular Ca2+-overload are considered to explain I/R-induced injury to the heart. However, it is becoming apparent that oxidative stress is the most critical pathogenic factor because it produces myocardial abnormalities directly or indirectly for the occurrence of cardiac damage. Furthermore, I/R injury has been shown to generate oxidative stress by promoting the formation of different reactive oxygen species due to defects in mitochondrial function and depressions in both endogenous antioxidant levels as well as regulatory antioxidative defense systems. It has also been demonstrated to adversely affect a wide variety of metabolic pathways and targets in cardiomyocytes, various resident structures in myocardial interstitium, as well as circulating neutrophils and leukocytes. These I/R-induced alterations in addition to myocardial inflammation may cause cell death, fibrosis, inflammation, Ca2+-handling abnormalities, activation of proteases and phospholipases, as well as subcellular remodeling and depletion of energy stores in the heart. Analysis of results from isolated hearts perfused with or without some antioxidant treatments before subjecting to I/R injury has indicated that cardiac dysfunction is associated with the development of oxidative stress, intracellular Ca2+-overload and protease activation. In addition, changes in the sarcolemma and sarcoplasmic reticulum Ca2+-handling, mitochondrial oxidative phosphorylation as well as myofibrillar Ca2+-ATPase activities in I/R hearts were attenuated by pretreatment with antioxidants. The I/R-induced alterations in cardiac function were simulated upon perfusing the hearts with oxyradical generating system or oxidant. These observations support the view that oxidative stress may be intimately involved in inducing intracellular Ca2+-overload, protease activation, subcellular remodeling, and cardiac dysfunction as a consequence of I/R injury to the heart.

CircBCL2L13 attenuates cardiomyocyte oxidative stress and apoptosis in cardiac ischemia‒reperfusion injury via miR‐1246/PEG3 signaling

“…[21] When pathological I/R injury is triggered, oxidative stress and mitochondrial damage can occur in cardiomyocytes, leading to cardiomyocyte apoptosis and even death. [22] A significant increase in circBCL2L13 expression was observed in our study using in vivo I/R and in vitro OGD/R models. Taken together, these findings suggest that circBCL2L13 plays a role in modulating the cardiomyocyte phenotype after I/R injury.…”

Engineering a conduction-consistent cardiac patch with rGO/PLCL electrospun nanofibrous membranes and human iPSC-derived cardiomyocytes

“…The relative antioxidant activity increased nearly 50 fold in the 8 wt% and nearly 30 fold in the 2 wt% rGO/PLCL group compared to the group without rGO. Therefore, rGO membranes can effectively resist reactive oxygen species, which is extremely beneficial for the survival of myocardial cells on membranes ( Dhalla et al, 2022 ).…”

Pharmacological Modulation by Low Molecular Weight Heparin of Purinergic Signaling in Cardiac Cells Prevents Arrhythmia and Lethality Induced by Myocardial Infarction

“…The use of animal models of CIR to reproduce AMI in the laboratory has contributed to the elucidation of molecular mechanisms and to the development of new cardioprotective strategies to prevent the death of patients affected by ischemic myocardial diseases. Reperfusion-induced cardiac injuries include arrhythmias, myocardial stunning, micro-vascular dysfunction, and cell death [ 3 , 5 , 6 , 7 ]. Oxidative stress, calcium overload, and inflammation have all been implicated as injury mechanisms, which act synergistically: oxidative stress can lead to calcium overload, and both can lead to cell death [ 5 , 6 , 7 , 8 ].…”

“…Reperfusion-induced cardiac injuries include arrhythmias, myocardial stunning, micro-vascular dysfunction, and cell death [ 3 , 5 , 6 , 7 ]. Oxidative stress, calcium overload, and inflammation have all been implicated as injury mechanisms, which act synergistically: oxidative stress can lead to calcium overload, and both can lead to cell death [ 5 , 6 , 7 , 8 ]. Phosphorylation of ryanodine receptor 2 (RyR2) by Ca 2+ calmodulin-dependent kinase II (CaMKII) was previously shown as a key mechanism related to Ca 2+ disfunction and arrhythmias in CIR [ 9 ], and, later, redox modifications of RyR2 were seen to concur with phosphorylation in arrhythmogenesis [ 10 ].…”