title: NADPH oxidases and cardiac remodelling.
abstract: A heart under chronic stress undergoes cardiac remodelling, a process that comprises structural and functional changes including cardiomyocyte hypertrophy, interstitial fibrosis, contractile dysfunction, cell death and ventricular dilatation. Reactive oxygen species (ROS)-dependent modulation of intracellular signalling is implicated in the development of cardiac remodelling. Among the different ROS sources that are present in the heart, NADPH oxidases (NOXs) are particularly important in redox signalling. NOX isoforms are expressed in multiple cell types including cardiomyocytes, fibroblasts, endothelial cells and inflammatory cells-with the two main isoforms expressed in the heart being NOX2 and NOX4. Recent studies indicate that NOX-dependent signalling is involved in the development of cardiomyocyte hypertrophy, interstitial fibrosis and post-MI remodelling. NOXs may also be involved in the genesis of contractile dysfunction and myocyte apoptosis. Here, we review the main effects of NOXs in the pathogenesis of cardiac remodelling and the redox-sensitive signalling pathways that underlie these effects. The elucidation of mechanisms involved in NOX-dependent regulation of cardiac remodelling may lead to new therapeutic targets for heart failure.
authors.affiliation: Cardiovascular Division, King's College London British Heart Foundation Centre, London, SE5 9PJ, UK.
authors.forename: Adam
authors.initials: A
authors.lastname: Nabeebaccus
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Ajay M
authors.initials: AM
authors.lastname: Shah
mesh_terms: D017209:Apoptosis; D006328:Cardiac Catheterization; D004730:Endothelium, Vascular; D005347:Fibroblasts / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors; D020257:Ventricular Remodeling
chemical_list: D017382:Reactive Oxygen Species; D019255:NADPH Oxidases