© 2000 American Heart Association, Inc.
Editorials |
Vascular gp91phox
Beyond the Endothelium
From the Hypertension & Vascular Research Division, Henry Ford Hospital, Detroit, Mich.
Correspondence to Patrick J. Pagano, E & R Building, Room 7044, Hypertension & Vascular Research Division, Henry Ford Hospital, 2799 Grand Blvd, Detroit, MI 43202. E-mail ppagano1@hfhs.org
Key Words: reactive oxygen species • superoxide • NAD(P)H oxidoreductases • muscle, smooth • endothelium • fibroblast
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Introduction |
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In this issue of Circulation Research, Görlach et al1 present compelling evidence for conventional gp91phox-containing NAD(P)H oxidase in the vascular endothelium and for the functional involvement of gp91phox in endothelial cell NAD(P)H oxidase superoxide anion (O2–) production and aberrant endothelium-dependent relaxation. Many studies have implicated reactive oxygen species in the impairment of endothelium-dependent vascular responses.2 3 4 5 6 7 8 9 10 Since their initial discovery in the vasculature and the suggestion of their importance in the modulation of endothelium-derived relaxing factor nitric oxide (EDRF/NO) bioactivity, phagocyte-like NAD(P)H oxidases have been under intense study in 3 major vascular cell types.11 12 13 14 15 16 17 18 Griendling et al19 showed the presence of angiotensin II (Ang II)–activatable NAD(P)H oxidase in rat vascular smooth muscle, and Mohazzab-H and colleagues12 14 also made seminal discoveries of endothelial and smooth muscle isotypes in bovine arteries. Because of the juxtaposition of these important sources of O2- near the sites of release and action of EDRF/NO, most interest in vascular biology has concerned components in these 2 cell types. Additional studies have demonstrated molecular evidence for most NAD(P)H oxidase components in both cell types,13 15 16 20 whereas there has been scant evidence for gp91phox in vascular smooth muscle, although a homologue, mox1, has been suggested to stand in for gp91phox.21 In addition, my colleagues and I have shown that the vascular adventitia contains 4 phagocyte-like components, including gp91phox,9 10 18 and that rabbit adventitial fibroblasts contain an NAD(P)H oxidase functionally similar to the phagocyte oxidase.18 Recently, we screened a cDNA library prepared from these fibroblasts and obtained an
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