Cellular redox dysfunction in the development of cardiovascular diseases

• Published in: Biochimica et biophysica acta. General subjects Vol. 1861; no. 11; pp. 2822 - 2829
• Main Authors: Kanaan, Georges N., Harper, Mary-Ellen
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2017
• Subjects: adenosine triphosphate; Antioxidants - metabolism; arrhythmia; atherosclerosis; beta oxidation; Cardiac pathologies; Cardiovascular Diseases - genetics; Cardiovascular Diseases - metabolism; Cardiovascular Diseases - pathology; Energy Metabolism; Fatty Acids - metabolism; Glutathione; Heart; heart failure; Humans; hydrogen peroxide; Hydrogen Peroxide - metabolism; hydroxyl radicals; hypertension; hypertrophy; Mitochondria; Mitochondria - metabolism; myocardial ischemia; nitric oxide; Nitric Oxide - metabolism; nitrogen; nitrogen dioxide; Oxidation-Reduction; Oxidative phosphorylation; Oxidative stress; Oxidative Stress - genetics; oxygen; Oxygen - metabolism; reactive nitrogen species; Reactive oxygen species; Reactive Oxygen Species - metabolism; Redox; Signal Transduction; Heart; Oxidative stress; Mitochondria; Reactive oxygen species; Oxidative phosphorylation; Redox; Cardiac pathologies; Glutathione
• ISSN: 0304-4165; 1872-8006
• DOI: 10.1016/j.bbagen.2017.07.027

To meet its exceptionally high energy demands, the heart relies largely on fatty acid oxidation, which then drives the oxidative phosphorylation system in mitochondria. Each day, this system produces about 6kg of ATP to sustain heart function. Fatty acid oxidation is sometimes associated with high rates of mitochondrial reactive oxygen species (ROS) production. By definition, ROS are singlet electron intermediates formed during the partial reduction of oxygen to water and they include radical and non-radical intermediates like superoxide, hydrogen peroxide and hydroxyl radical. Superoxide can also interact with nitric oxide to produce peroxynitrite that in turn can give rise to other radical or non-radical reactive nitrogen species (RNS) like nitrogen dioxide, dinitrogen trioxide and others. While mitochondrial and cellular functions can be impaired by ROS if they accumulate, under normal physiological conditions ROS are important signaling molecules in the cardiovascular system. A fine balance between ROS production and antioxidant systems, including glutathione redox, is essential in the heart; otherwise the ensuing damage can contribute to pathogenic processes, which can culminate in endothelial dysfunction, atherosclerosis, hypertension, cardiac hypertrophy, arrhythmias, myocardial ischemia/reperfusion damage, and heart failure. Here we provide a succinct review of recent findings. •Impaired redox mechanisms can lead to excessive production of reactive species.•Reactive species include reactive oxygen species (ROS) and nitrogen species (RNS).•Physiologic levels of reactive species have important signaling functions.•Excessive levels of reactive species contribute to cardiovascular disease development.