Translating the oxidative stress hypothesis into the clinic: NOX versus NOS
Open Access
- 16 October 2009
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Molecular Medicine
- Vol. 87 (11), 1071-1076
- https://doi.org/10.1007/s00109-009-0544-2
Abstract
Cardiovascular diseases remain the leading cause of death in industrialised nations. Since the pathomechanisms of most cardiovascular diseases are not understood, the majority of therapeutic approaches are symptom-orientated. Knowing the molecular mechanism of disease would enable more targeted therapies. One postulated underlying mechanism of cardiovascular diseases is oxidative stress, i.e. the increased occurrence of reactive oxygen species such as superoxide. Oxidative stress leads to a dysfunction of vascular endothelium-dependent protective mechanisms. There is growing evidence that this scenario also involves impaired nitric oxide (NO)-cyclic GMP signalling. Out of a number of enzyme families that can produce reactive oxygen species, NADPH oxidases stand out, as they are the only enzymes whose sole purpose is to produce reactive oxygen species. This review focuses on the clinically validated targets of oxidative stress, NO synthase (NOS) and the NO receptor, soluble guanylate cyclase as well as the source of ROS, e.g. NADPH oxidases. We place recent knowledge in the function and regulation of these enzyme families into clinical perspective. For a comprehensive overview of the biology and pharmacology of oxidative stress and possible other sources and targets, we refer to other literature overviews.Keywords
This publication has 49 references indexed in Scilit:
- Nox proteins in signal transductionFree Radical Biology & Medicine, 2009
- Selective targeting of NADPH oxidase for cardiovascular protectionCurrent Opinion in Pharmacology, 2009
- Vascular protection by tetrahydrobiopterin: progress and therapeutic prospectsTrends in Pharmacological Sciences, 2009
- Calcium-Dependent NOX5 Nicotinamide Adenine Dinucleotide Phosphate Oxidase Contributes to Vascular Oxidative Stress in Human Coronary Artery DiseaseJournal of the American College of Cardiology, 2008
- Nox enzymes, ROS, and chronic disease: An example of antagonistic pleiotropyFree Radical Biology & Medicine, 2007
- Basic Mechanisms of Oxidative Stress and Reactive Oxygen Species in Cardiovascular InjuryTrends in Cardiovascular Medicine, 2007
- Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vesselsJCI Insight, 2006
- NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potentialNature Reviews Drug Discovery, 2006
- Novel Nox inhibitor of oxLDL-induced reactive oxygen species formation in human endothelial cellsBiochemical and Biophysical Research Communications, 2006
- Molecular composition and regulation of the Nox family NAD(P)H oxidasesBiochemical and Biophysical Research Communications, 2005