doi: 10.1161/01.RES.0000066880.62205.B0
© 2003 American Heart Association, Inc.
Editorials |
A Radical Adventure
The Quest for Specific Functions and Inhibitors of Vascular NAPDH Oxidases
From the Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Frankfurt am Main, Germany.
Correspondence to Ralf P. Brandes, Institut für Kardiovaskuläre Physiologie, Klinikum der J.W. Goethe-Universität, Theodor-Stern-Kai 7, D-60596 Frankfurt am Main, Germany. E-mail r.brandes@em.uni-frankfurt.de
Key Words: oxidative stress • NADPH oxidase • restenosis • neointima
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
Over the past two decades, the number of scientific publications addressing the role of oxidative stress in physiology and pathophysiology has increased exponentially. Almost all cardiovascular disease states including hypertension, hyperlipidemia, diabetes, arteriosclerosis, unstable angina, vasculitis and myocarditis, restenosis as well as ischemia/reperfusion have been linked to an enhanced generation of oxygen-derived free radicals.1 Consequently, oxidative stress is generally considered to be a major progression factor for cardiovascular disease, despite the fact that the majority of the large prospective, controlled trials have failed to uncover a beneficial effect of antioxidative treatment.2
Therefore, one is left to wonder, whether an unspecific antioxidative radical scavenging approach is suitable to substantially lower oxidative stress and to affect disease progression. Indeed, individual sources of oxidative stress and the contribution of these enzymes to disease progression have to be identified. This approach may ultimately lead to the development of "specific" inhibitors of oxidative stress to target the intracellular source of free radical generation.
An important source of oxygen-derived radical generation are the NADPH oxidases, ubiquitous to all vascular cells.3 These enzymes, which in their subunit composition are either similar or even identical to the leukocyte NADPH oxidase can be induced and activated by many factors involved in the initiation and progression of cardiovascular disease such as thrombin, tumor necrosis factor-
, platelet-derived growth factor, and proatherosclerotic lipids such as lysophosphatidyl choline and Lp(a). The best characterized stimulus for NADPH oxidase activation and induction is angiotensin II, and experiments utilizing mice lacking different NADPH oxidase subunits