Circulation. 2002;105:1429-1435
Published online before print March 4, 2002, doi: 10.1161/01.CIR.0000012917.74432.66
Published online before print March 4, 2002, doi: 10.1161/01.CIR.0000012917.74432.66
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(Circulation. 2002;105:1429.)
© 2002 American Heart Association, Inc.
Superoxide Production and Expression of Nox Family Proteins in Human Atherosclerosis
From the Department of Medicine (D.S., D.W., B.L., R.E.C., K.S., G.P.S., L.V., W.R.T., K.K.G.), Division of Cardiology, Department of Pathology and Laboratory Medicine (J.D.L.), and Department of Surgery (J.D.V.), Emory University, Atlanta, Ga, and the Department of Veterinary Molecular Biology (M.T.Q.), Montana State University, Bozeman, Mont.
Correspondence to Dr Kathy K. Griendling, Emory University, Division of Cardiology, 319 WMB, 1639 Pierce Dr, Atlanta, GA 30322. E-mail kgriend{at}emory.edu
Background— NAD(P)H oxidases are important sources of superoxide in the vasculature, the activity of which is associated with risk factors for human atherosclerosis. This study was designed to investigate the localization of superoxide production and the expression of the Nox family of NAD(P)H oxidase proteins (gp91phox, Nox1, and Nox4) in nonatherosclerotic and atherosclerotic human coronary arteries.
Methods and Results— In coronary artery segments from explanted human hearts, we examined intracellular superoxide production with dihydroethidium. In nonatherosclerotic coronary arteries, superoxide was present homogenously throughout the intima, media, and adventitia. In atherosclerotic arteries, there was an additional intense area of superoxide in the plaque shoulder, which is rich in macrophages and 
-actin–positive cells. p22phox colocalized with gp91phox mainly in macrophages, whereas Nox4 was found only in nonphagocytic vascular cells. Expression of gp91phox and p22phox mRNA was associated with the severity of atherosclerosis. gp91phox correlated with the plaque macrophage content, whereas Nox4 correlated with the content of -actin–positive cells. Nox1 expression was low both in human coronary arteries and isolated vascular cells.
Conclusions— Several Nox proteins, including gp91phox and Nox4, may contribute to increased intracellular oxidative stress in human coronary atherosclerosis in a cell-specific manner and thus may be involved in the genesis and progression of human coronary atherosclerotic disease.
Key Words: enzymes • coronary disease • arteries • atherosclerosis
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J. F. Keaney Jr Oxidative Stress and the Vascular Wall: NADPH Oxidases Take Center Stage Circulation, October 25, 2005; 112(17): 2585 - 2588. [Full Text] [PDF]
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C. S. Wilcox Oxidative stress and nitric oxide deficiency in the kidney: a critical link to hypertension? Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R913 - R935. [Abstract] [Full Text] [PDF]
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Y. M. Kim, T. J. Guzik, Y. H. Zhang, M. H. Zhang, H. Kattach, C. Ratnatunga, R. Pillai, K. M. Channon, and B. Casadei A Myocardial Nox2 Containing NAD(P)H Oxidase Contributes to Oxidative Stress in Human Atrial Fibrillation Circ. Res., September 30, 2005; 97(7): 629 - 636. [Abstract] [Full Text] [PDF]
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 C. Espinola-Klein, S. Blankenberg, and T. Munzel Editorial Comment--Is Heme Oxygenase-1 a Causal Player for Plaque Stability? Stroke, September 1, 2005; 36(9): 1901 - 1903. [Full Text] [PDF]
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H. Sato, M. Sato, H. Kanai, T. Uchiyama, T. Iso, Y. Ohyama, H. Sakamoto, J. Tamura, R. Nagai, and M. Kurabayashi Mitochondrial reactive oxygen species and c-Src play a critical role in hypoxic response in vascular smooth muscle cells Cardiovasc Res, September 1, 2005; 67(4): 714 - 722. [Abstract] [Full Text] [PDF]
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M. S. Wolin, M. Ahmad, and S. A. Gupte Oxidant and redox signaling in vascular oxygen sensing mechanisms: basic concepts, current controversies, and potential importance of cytosolic NADPH Am J Physiol Lung Cell Mol Physiol, August 1, 2005; 289(2): L159 - L173. [Abstract] [Full Text] [PDF]
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T. Munzel, A. Daiber, V. Ullrich, and A. Mulsch Vascular Consequences of Endothelial Nitric Oxide Synthase Uncoupling for the Activity and Expression of the Soluble Guanylyl Cyclase and the cGMP-Dependent Protein Kinase Arterioscler Thromb Vasc Biol, August 1, 2005; 25(8): 1551 - 1557. [Abstract] [Full Text] [PDF]
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S. Kinugawa, J. Zhang, E. Messina, E. Walsh, H. Huang, P. M. Kaminski, M. S. Wolin, and T. H. Hintze gp91phox-containing NAD(P)H oxidase mediates attenuation of nitric oxide-dependent control of myocardial oxygen consumption by ANG II Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H862 - H867. [Abstract] [Full Text] [PDF]
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G. Zalba, O. Beloqui, G. S. Jose, M. U. Moreno, A. Fortuno, and J. Diez NADPH Oxidase-Dependent Superoxide Production Is Associated With Carotid Intima-Media Thickness in Subjects Free of Clinical Atherosclerotic Disease Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1452 - 1457. [Abstract] [Full Text] [PDF]
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M. Akishita, K. Nagai, H. Xi, W. Yu, N. Sudoh, T. Watanabe, M. Ohara-Imaizumi, S. Nagamatsu, K. Kozaki, M. Horiuchi, et al. Renin-Angiotensin System Modulates Oxidative Stress-Induced Endothelial Cell Apoptosis in Rats Hypertension, June 1, 2005; 45(6): 1188 - 1193. [Abstract] [Full Text] [PDF]
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F. Krotz, B. Engelbrecht, M. A. Buerkle, F. Bassermann, H. Bridell, T. Gloe, J. Duyster, U. Pohl, and H.-Y. Sohn The Tyrosine Phosphatase, SHP-1, Is a Negative Regulator of Endothelial Superoxide Formation J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1700 - 1706. [Abstract] [Full Text] [PDF]
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 H. Zhao, J. Joseph, H. M. Fales, E. A. Sokoloski, R. L. Levine, J. Vasquez-Vivar, and B. Kalyanaraman Detection and characterization of the product of hydroethidine and intracellular superoxide by HPLC and limitations of fluorescence PNAS, April 19, 2005; 102(16): 5727 - 5732. [Abstract] [Full Text] [PDF]
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L. Cheng, W. Cao, J. Behar, P. Biancani, and K. M. Harnett Inflammation induced changes in arachidonic acid metabolism in cat LES circular muscle Am J Physiol Gastrointest Liver Physiol, April 1, 2005; 288(4): G787 - G797. [Abstract] [Full Text] [PDF]
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J. Hwang, D. J. Kleinhenz, B. Lassegue, K. K. Griendling, S. Dikalov, and C. M. Hart Peroxisome proliferator-activated receptor-{gamma} ligands regulate endothelial membrane superoxide production Am J Physiol Cell Physiol, April 1, 2005; 288(4): C899 - C905. [Abstract] [Full Text] [PDF]
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V. Adams, A. Linke, N. Krankel, S. Erbs, S. Gielen, S. Mobius-Winkler, J. F. Gummert, F. W. Mohr, G. Schuler, and R. Hambrecht Impact of Regular Physical Activity on the NAD(P)H Oxidase and Angiotensin Receptor System in Patients With Coronary Artery Disease Circulation, February 8, 2005; 111(5): 555 - 562. [Abstract] [Full Text] [PDF]
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T. Kawahara, M. Kohjima, Y. Kuwano, H. Mino, S. Teshima-Kondo, R. Takeya, S. Tsunawaki, A. Wada, H. Sumimoto, and K. Rokutan Helicobacter pylori lipopolysaccharide activates Rac1 and transcription of NADPH oxidase Nox1 and its organizer NOXO1 in guinea pig gastric mucosal cells Am J Physiol Cell Physiol, February 1, 2005; 288(2): C450 - C457. [Abstract] [Full Text] [PDF]
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S. H.M. Ellmark, G. J. Dusting, M. Ng Tang Fui, N. Guzzo-Pernell, and G. R. Drummond The contribution of Nox4 to NADPH oxidase activity in mouse vascular smooth muscle Cardiovasc Res, February 1, 2005; 65(2): 495 - 504. [Abstract] [Full Text] [PDF]
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K. Laude, H. Cai, B. Fink, N. Hoch, D. S. Weber, L. McCann, G. Kojda, T. Fukai, H. H. H. W. Schmidt, S. Dikalov, et al. Hemodynamic and biochemical adaptations to vascular smooth muscle overexpression of p22phox in mice Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H7 - H12. [Abstract] [Full Text] [PDF]
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S. A. Gupte, P. M. Kaminski, B. Floyd, R. Agarwal, N. Ali, M. Ahmad, J. Edwards, and M. S. Wolin Cytosolic NADPH may regulate differences in basal Nox oxidase-derived superoxide generation in bovine coronary and pulmonary arteries Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H13 - H21. [Abstract] [Full Text] [PDF]
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R. P. Brandes and J. Kreuzer Vascular NADPH oxidases: molecular mechanisms of activation Cardiovasc Res, January 1, 2005; 65(1): 16 - 27. [Abstract] [Full Text] [PDF]
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 E. Pedruzzi, C. Guichard, V. Ollivier, F. Driss, M. Fay, C. Prunet, J.-C. Marie, C. Pouzet, M. Samadi, C. Elbim, et al. NAD(P)H Oxidase Nox-4 Mediates 7-Ketocholesterol-Induced Endoplasmic Reticulum Stress and Apoptosis in Human Aortic Smooth Muscle Cells Mol. Cell. Biol., December 15, 2004; 24(24): 10703 - 10717. [Abstract] [Full Text] [PDF]
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J.-M. Li and A. M Shah Endothelial cell superoxide generation: regulation and relevance for cardiovascular pathophysiology Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2004; 287(5): R1014 - R1030. [Abstract] [Full Text] [PDF]
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G. P. Sorescu, H. Song, S. L. Tressel, J. Hwang, S. Dikalov, D. A. Smith, N. L. Boyd, M. O. Platt, B. Lassegue, K. K. Griendling, et al. Bone Morphogenic Protein 4 Produced in Endothelial Cells by Oscillatory Shear Stress Induces Monocyte Adhesion by Stimulating Reactive Oxygen Species Production From a Nox1-Based NADPH Oxidase Circ. Res., October 15, 2004; 95(8): 773 - 779. [Abstract] [Full Text] [PDF]
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 R. Stocker and J. F. Keaney Jr. Role of Oxidative Modifications in Atherosclerosis Physiol Rev, October 1, 2004; 84(4): 1381 - 1478. [Abstract] [Full Text] [PDF]
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M. T. Quinn and K. A. Gauss Structure and regulation of the neutrophil respiratory burst oxidase: comparison with nonphagocyte oxidases J. Leukoc. Biol., October 1, 2004; 76(4): 760 - 781. [Abstract] [Full Text] [PDF]
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S. Wassmann, K. Wassmann, and G. Nickenig Modulation of Oxidant and Antioxidant Enzyme Expression and Function in Vascular Cells Hypertension, October 1, 2004; 44(4): 381 - 386. [Abstract] [Full Text] [PDF]
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M. Yokoyama and N. Inoue How Vascular NAD(P)H Oxidase Activity and Nox Isoform Expression are Regulated Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1540 - 1541. [Full Text] [PDF]
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T. J. Guzik, J. Sadowski, B. Kapelak, A. Jopek, P. Rudzinski, R. Pillai, R. Korbut, and K. M. Channon Systemic Regulation of Vascular NAD(P)H Oxidase Activity and Nox Isoform Expression in Human Arteries and Veins Arterioscler Thromb Vasc Biol, September 1, 2004; 24(9): 1614 - 1620. [Abstract] [Full Text] [PDF]
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Z. Chen, J. F. Keaney Jr., E. Schulz, B. Levison, L. Shan, M. Sakuma, X. Zhang, C. Shi, S. L. Hazen, and D. I. Simon Decreased neointimal formation in Nox2-deficient mice reveals a direct role for NADPH oxidase in the response to arterial injury PNAS, August 31, 2004; 101(35): 13014 - 13019. [Abstract] [Full Text] [PDF]
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