Modulations of Cardiac Functions and Pathogenesis by Reactive Oxygen Species and Natural Antioxidants

Abstract

Homeostasis in the level of reactive oxygen species (ROS) in cardiac myocytes plays a critical role in regulating their physiological functions. Disturbance of balance between generation and removal of ROS is a major cause of cardiac myocyte remodeling, dysfunction, and failure. Cardiac myocytes possess several ROS-producing pathways, such as mitochondrial electron transport chain, NADPH oxidases, and nitric oxide synthases, and have endogenous antioxidation mechanisms. Cardiac Ca2+-signaling toolkit proteins, as well as mitochondrial functions, are largely modulated by ROS under physiological and pathological conditions, thereby producing alterations in contraction, membrane conductivity, cell metabolism and cell growth and death. Mechanical stresses under hypertension, post-myocardial infarction, heart failure, and valve diseases are the main causes for stress-induced cardiac remodeling and functional failure, which are associated with ROS-induced pathogenesis. Experimental evidence demonstrates that many cardioprotective natural antioxidants, enriched in foods or herbs, exert beneficial effects on cardiac functions (Ca2+ signal, contractility and rhythm), myocytes remodeling, inflammation and death in pathological hearts. The review may provide knowledge and insight into the modulation of cardiac pathogenesis by ROS and natural antioxidants.

Therapeutic Targets for Regulating Oxidative Damage Induced by Ischemia-Reperfusion Injury: A Study from a Pharmacological Perspective

“…The scientific community accepts the role of ROS and other important free radicals, such as superoxide radical (O2), formed by adding extra electrons in an oxygen molecule (OH), which is created from O 2 via the interaction of H 2 O catalyzed by transition metals including iron in I-R [ 62 ]. Oxygen radicals can be formed by the action of singlet oxygen, which commonly occurs in ischemic tissues [ 63 ]. The eukaryotic cell has a defense system similar to that of enzymes, such as superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx), and glutathione reductase, which inhibit reactive species formation [ 64 , 65 ] For example, the concentrations of SOD1, SOD2, CAT, and GSH-Px decrease in I-R [ 66 , 67 ].…”

Engineering Injectable Anti‐Inflammatory Hydrogels to Treat Acute Myocardial Infarction

“…Oxidative stress is responsible for cardiovascular diseases and is related to the pathogenesis of ischemic heart disease and HF. [ 66 ] ROS, which contain at least one oxygen atom, are highly reactive molecules [ 67 ] and are produced as byproducts of mitochondrial respiration and metabolism. [ 68 ] They are commonly classified as either free radicals with unpaired electrons, such as superoxide anions, or nonradical derivatives, such as hydrogen peroxide (H 2 O 2 ).…”

“…[ 78 ] ROS can activate the NF‐κB signaling pathway and upregulate tumor necrosis factor‐α (TNF‐α). [ 67 ] Myeloid differentiation protein 2 binds to Toll‐like receptor 4 (TLR4) to activate it and mediate inflammation in AMI. [ 79 ] The complex combines with the myeloid differentiation factor 88 adaptor protein and triggers receptor complex interaction with TNF receptor‐associated factor 6 and transforming growth factor‐activated kinase 1.…”

Inhibition of mitochondrial respiration has fundamentally different effects on proliferation, cell survival and stress response in immature versus differentiated cardiomyocyte cell lines

“…The latter can lead to DNA, protein and lipid oxidation thereby impairing intracellular homeostasis and leading to oxidative stress. Whereas cells have a certain capacity for ROS detoxification to outlast periods of unfavorable growth conditions, prolonged or excessive oxidative damage can eventually result in cell death (Woo et al, 2021). Given the limited regenerative potential of the postnatal mammalian heart, loss of cardiomyocytes as a result of mitochondrial dysfunction contributes to impairment of heart function during various cardiovascular diseases.…”