Translating the oxidative stress hypothesis into the clinic: NOX versus NOS.
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.
Armitage
Melanie E
ME
Centre for Vascular Health, Department of Pharmacology, Monash University, Building 13E, Wellington Rd, Clayton, Victoria 3800, Australia.
Wingler
Kirstin
K
Schmidt
Harald H H W
HH
La
Mylinh
M
D000818:Animals; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D019255:NADPH Oxidases / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D000071756:Soluble Guanylyl Cyclase
D017382:Reactive Oxygen Species; D018160:Receptors, Cytoplasmic and Nuclear; D019001:Nitric Oxide Synthase; D019255:NADPH Oxidases; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase