Vascular effects following homozygous disruption of p47phox -: An essential component of NADPH oxidase

被引:127
作者
Hsich, E
Segal, BH
Pagano, PJ
Rey, FE
Paigen, B
Deleonardis, J
Hoyt, RF
Holland, SM
Finkel, T
机构
[1] NHLBI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA
[2] NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA
[3] NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA
[4] Jackson Lab, Bar Harbor, ME 04609 USA
[5] Henry Ford Hosp, Hypertens & Vasc Res Div, Detroit, MI 48202 USA
关键词
apolipoproteins; atherosclerosis; blood pressure;
D O I
10.1161/01.CIR.101.11.1234
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-Evidence suggests that the vessel wall contains an oxidase similar, if not identical, to phagocytic NADPH oxidase, We tested the contribution of this specific oxidase to the progression of atherosclerosis and the regulation of blood pressure. Methods and Results-An examination of aortic rings from wild-type mice and mice with homozygous targeted disruptions in p47(phox) revealed that p47(phox) knockout mice had a reduction in vascular superoxide production. However, analyses of apoE -/- p47(phox) +/+ and apoE -/- p47p(hox) -/- strains of mice demonstrated no significant differences in atherosclerotic lesion sizes. Similarly, analyses of wild-type and p47(phox) knockout mice revealed no differences in either basal blood pressure or the rise in blood pressure seen after the pharmacological inhibition of nitric oxide synthase, Conclusions-NADPH oxidase contributes to basal vascular superoxide production. However, the absence of a functional oxidase does not significantly affect the progression of atherosclerosis in the standard mouse apoE -/- model, nor does it significantly influence basal blood pressure.
引用
收藏
页码:1234 / 1236
页数:3
相关论文
共 23 条
[1]   O2 sensing is preserved in mice lacking the gp91 phox subunit of NADPH oxidase [J].
Archer, SL ;
Reeve, HL ;
Michelakis, E ;
Puttagunta, L ;
Waite, R ;
Nelson, DP ;
Dinauer, MC ;
Weir, EK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (14) :7944-7949
[2]   Expression of NADH/NADPH oxidase p22phox in human coronary arteries [J].
Azumi, H ;
Inoue, N ;
Takeshita, S ;
Rikitake, Y ;
Kawashima, S ;
Hayashi, Y ;
Itoh, H ;
Yokoyama, M .
CIRCULATION, 1999, 100 (14) :1494-1498
[3]  
De Keulenaer GW, 1998, BIOCHEM J, V329, P653
[4]   Assembly of the phagocyte NADPH oxidase: Molecular interaction of oxidase proteins [J].
DeLeo, FR ;
Quinn, MT .
JOURNAL OF LEUKOCYTE BIOLOGY, 1996, 60 (06) :677-691
[5]   p22phox mRNA expression and NADPH oxidase activity are increased in aortas from hypertensive rats [J].
Fukui, T ;
Ishizaka, N ;
Rajagopalan, S ;
Lauren, JB ;
Capers, Q ;
Taylor, WR ;
Harrison, DG ;
deLeon, H ;
Wilcox, JN ;
Griendling, KK .
CIRCULATION RESEARCH, 1997, 80 (01) :45-51
[6]   ANGIOTENSIN-II STIMULATES NADH AND NADPH OXIDASE ACTIVITY IN CULTURED VASCULAR SMOOTH-MUSCLE CELLS [J].
GRIENDLING, KK ;
MINIERI, CA ;
OLLERENSHAW, JD ;
ALEXANDER, RW .
CIRCULATION RESEARCH, 1994, 74 (06) :1141-1148
[7]   NADH/NADPH oxidase and vascular function [J].
Griendling, KK ;
UshioFukai, M .
TRENDS IN CARDIOVASCULAR MEDICINE, 1997, 7 (08) :301-307
[8]   PHYSIOLOGICAL CONSEQUENCES OF INCREASED VASCULAR OXIDANT STRESSES IN HYPERCHOLESTEROLEMIA AND ATHEROSCLEROSIS - IMPLICATIONS FOR IMPAIRED VASOMOTION [J].
HARRISON, DG ;
OHARA, Y .
AMERICAN JOURNAL OF CARDIOLOGY, 1995, 75 (06) :B75-B81
[9]   THE P47(PHOX) MOUSE KNOCK-OUT MODEL OF CHRONIC GRANULOMATOUS-DISEASE [J].
JACKSON, SH ;
GALLIN, JI ;
HOLLAND, SM .
JOURNAL OF EXPERIMENTAL MEDICINE, 1995, 182 (03) :751-758
[10]   Superoxide anion production is increased in a model of genetic hypertension - Role of the endothelium [J].
Kerr, S ;
Brosnan, MJ ;
McIntyre, M ;
Reid, JL ;
Dominiczak, AF ;
Hamilton, CA .
HYPERTENSION, 1999, 33 (06) :1353-1358