The Role of Oxidative Stress in Cardiac Disease: From Physiological Response to Injury Factor

Figure 2

Role of the ROS system in the heart in physiology and disease. ROS are oxygen-based chemical species characterized by high reactivity, and they include H₂O₂, OH^-, O₂^-, and ONOO^-. The most important cardiac ROS sources are mitochondria, xanthine oxidoreductase, uncoupled nitric oxide synthases, NADPH oxidase, cytochrome P450, and monoamine oxidases. Multiple antioxidant defense systems counteract ROS accumulation by scavenging and converting ROS to nontoxic molecules. These systems are both enzymatic and nonenzymatic: enzymes include catalase, glutathione peroxidase (GSHPsx), and superoxide dismutase (SOD) and nonenzymatic antioxidants include vitamins C and E, beta-carotene, ubiquinone, lipoic acid, and urate. ROS represent important second messengers within the heart, since they are involved in multiple physiological processes including differentiation, proliferation, and excitation-contraction coupling. Oxidative stress is defined as a dysregulation between the production of ROS and the endogenous antioxidant defense mechanisms. ROS are also involved in the onset of some complications related to specific clinical settings, including chemotherapy-induced cardiotoxicity, postoperative atrial fibrillation, and diabetic cardiomyopathy. When ROS are in excess, they can induce impairment of DNA, proteins, and lipids; inactivation of NO; and organelle dysfunction leading to cardiomyocyte apoptosis and dysfunction, cardiac hypertrophy, myocardial ischemia-reperfusion, and heart failure. Multiple antioxidant therapies (inhibition of oxidative stress producers, improvement of endogenous antioxidant capacity, and supplementation of exogenous antioxidants) and statins have been tested in order to counteract oxidative stress-induced cardiac damages. DNA: deoxyribonucleic acid; GSHPsx: glutathione peroxidase; H₂O₂: hydrogen peroxide; MAO: monoamine oxidase; NADPH: nicotinamide adenine dinucleotide phosphate hydrogen; NO: nitric oxide; NOS: nitric oxide synthase; O₂^-: superoxide anion; OH^-: hydroxyl anion; ONOO^-: peroxynitrite; ROS: reactive oxygen species; SOD: superoxide dismutase; XOR: xanthine oxidoreductase.