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INVITED REVIEW
Emory University School of Medicine, Division of Cardiology, Atlanta, Georgia 30322
The importance of reactive oxygen species (ROS) in vascular physiology and pathology is becoming increasingly evident. All cell types in the vascular wall produce ROS derived from superoxide-generating protein complexes similar to the leukocyte NADPH oxidase. Specific features of the vascular enzymes include constitutive and inducible activities, substrate specificity, and intracellular superoxide production. Most phagocyte enzyme subunits are found in vascular cells, including the catalytic gp91phox (aka, nox2), which was the earliest member of the newly discovered nox family. However, smooth muscle frequently expresses nox1 rather than gp91phox, and nox4 is additionally present in all cell types. In cell culture, agonists increase ROS production by activating multiple signals, including protein kinase C and Rac, and by upregulating oxidase subunits. The oxidases are also upregulated in vascular disease and are involved in the development of atherosclerosis and a significant part of angiotensin II-induced hypertension, possibly via nox1 and nox4. Likewise, enhanced vascular oxidase activity is associated with diabetes. Therefore, members of this enzyme family appear to be important in vascular biology and disease and constitute promising targets for future therapeutic interventions.
NAPDH oxidase; superoxide; blood vessels; atherosclerosis; hypertension
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R. M. Touyz Mitochondrial Redox Control of Matrix Metalloproteinase Signaling in Resistance Arteries Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 685 - 688. [Full Text] [PDF]
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M. Menshikov, O. Plekhanova, H. Cai, K. Chalupsky, Y. Parfyonova, P. Bashtrikov, V. Tkachuk, and B. C. Berk Urokinase Plasminogen Activator Stimulates Vascular Smooth Muscle Cell Proliferation Via Redox-Dependent Pathways Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 801 - 807. [Abstract] [Full Text] [PDF]
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A. Sturrock, B. Cahill, K. Norman, T. P. Huecksteadt, K. Hill, K. Sanders, S. V. Karwande, J. C. Stringham, D. A. Bull, M. Gleich, et al. Transforming growth factor-beta1 induces Nox4 NAD(P)H oxidase and reactive oxygen species-dependent proliferation in human pulmonary artery smooth muscle cells Am J Physiol Lung Cell Mol Physiol, April 1, 2006; 290(4): L661 - L673. [Abstract] [Full Text] [PDF]
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D. Feliers, Y. Gorin, G. Ghosh-Choudhury, H. E. Abboud, and B. S. Kasinath Angiotensin II stimulation of VEGF mRNA translation requires production of reactive oxygen species Am J Physiol Renal Physiol, April 1, 2006; 290(4): F927 - F936. [Abstract] [Full Text] [PDF]
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M. Zhang, A. L. Kho, N. Anilkumar, R. Chibber, P. J. Pagano, A. M. Shah, and A. C. Cave Glycated Proteins Stimulate Reactive Oxygen Species Production in Cardiac Myocytes: Involvement of Nox2 (gp91phox)-Containing NADPH Oxidase Circulation, March 7, 2006; 113(9): 1235 - 1243. [Abstract] [Full Text] [PDF]
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P. L. Hordijk Regulation of NADPH Oxidases: The Role of Rac Proteins Circ. Res., March 3, 2006; 98(4): 453 - 462. [Abstract] [Full Text] [PDF]
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 J. A. Polikandriotis, H. L. Rupnow, S. C. Elms, R. E. Clempus, D. J. Campbell, R. L. Sutliff, L. A. S. Brown, D. M. Guidot, and C. M. Hart Chronic Ethanol Ingestion Increases Superoxide Production and NADPH Oxidase Expression in the Lung Am. J. Respir. Cell Mol. Biol., March 1, 2006; 34(3): 314 - 319. [Abstract] [Full Text] [PDF]
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X. Dai, X. Cao, and D. L. Kreulen Superoxide anion is elevated in sympathetic neurons in DOCA-salt hypertension via activation of NADPH oxidase Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1019 - H1026. [Abstract] [Full Text] [PDF]
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X.-Y. Yi, V. X. Li, F. Zhang, F. Yi, D. R. Matson, M. T. Jiang, and P.-L. Li Characteristics and actions of NAD(P)H oxidase on the sarcoplasmic reticulum of coronary artery smooth muscle Am J Physiol Heart Circ Physiol, March 1, 2006; 290(3): H1136 - H1144. [Abstract] [Full Text] [PDF]
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 R. Dechend, V. Homuth, G. Wallukat, D. N. Muller, M. Krause, J. Dudenhausen, H. Haller, and F. C. Luft Agonistic Antibodies Directed at the Angiotensin II, AT1 Receptor in Preeclampsia Reproductive Sciences, February 1, 2006; 13(2): 79 - 86. [Abstract] [PDF]
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L. Xia, H. Wang, H. J. Goldberg, S. Munk, I. G. Fantus, and C. I. Whiteside Mesangial cell NADPH oxidase upregulation in high glucose is protein kinase C dependent and required for collagen IV expression Am J Physiol Renal Physiol, February 1, 2006; 290(2): F345 - F356. [Abstract] [Full Text] [PDF]
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 D. Mehta and A. B. Malik Signaling Mechanisms Regulating Endothelial Permeability Physiol Rev, January 1, 2006; 86(1): 279 - 367. [Abstract] [Full Text] [PDF]
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M.-S. Zhou, I. H. Schulman, P. J. Pagano, E. A. Jaimes, and L. Raij Reduced NAD(P)H Oxidase in Low Renin Hypertension: Link Among Angiotensin II, Atherogenesis, and Blood Pressure Hypertension, January 1, 2006; 47(1): 81 - 86. [Abstract] [Full Text] [PDF]
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P. Persson A look back at a successful year Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1535 - R1535. [Full Text] [PDF]
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 J. Kuroda, K. Nakagawa, T. Yamasaki, K.-i. Nakamura, R. Takeya, F. Kuribayashi, S. Imajoh-Ohmi, K. Igarashi, Y. Shibata, K. Sueishi, et al. The superoxide-producing NAD(P)H oxidase Nox4 in the nucleus of human vascular endothelial cells Genes Cells, December 1, 2005; 10(12): 1139 - 1151. [Abstract] [Full Text] [PDF]
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N. E. Taylor and A. W. Cowley Jr. Effect of renal medullary H2O2 on salt-induced hypertension and renal injury Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1573 - R1579. [Abstract] [Full Text] [PDF]
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J.-Y. Park, R. E. Ferrell, J.-J. Park, J. M. Hagberg, D. A. Phares, J. M. Jones, and M. D. Brown NADPH oxidase p22phox gene variants are associated with systemic oxidative stress biomarker responses to exercise training J Appl Physiol, November 1, 2005; 99(5): 1905 - 1911. [Abstract] [Full Text] [PDF]
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N. Li, G. Zhang, F.-X. Yi, A.-P. Zou, and P.-L. Li Activation of NAD(P)H oxidase by outward movements of H+ ions in renal medullary thick ascending limb of Henle Am J Physiol Renal Physiol, November 1, 2005; 289(5): F1048 - F1056. [Abstract] [Full Text] [PDF]
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A. J. Begonja, S. Gambaryan, J. Geiger, B. Aktas, M. Pozgajova, B. Nieswandt, and U. Walter Platelet NAD(P)H-oxidase-generated ROS production regulates {alpha}IIb{beta}3-integrin activation independent of the NO/cGMP pathway Blood, October 15, 2005; 106(8): 2757 - 2760. [Abstract] [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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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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J. C McGrath, C. Deighan, A. M Briones, M. M. Shafaroudi, M. McBride, J. Adler, S. M Arribas, E. Vila, and C. J Daly New aspects of vascular remodelling: the involvement of all vascular cell types Exp Physiol, July 1, 2005; 90(4): 469 - 475. [Abstract] [Full Text] [PDF]
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R. M Touyz Intracellular mechanisms involved in vascular remodelling of resistance arteries in hypertension: role of angiotensin II Exp Physiol, July 1, 2005; 90(4): 449 - 455. [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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E. Qamirani, Y. Ren, L. Kuo, and T. W. Hein C-Reactive Protein Inhibits Endothelium-Dependent NO-Mediated Dilation in Coronary Arterioles by Activating p38 Kinase and NAD(P)H Oxidase Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 995 - 1001. [Abstract] [Full Text] [PDF]
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T. Ago, T. Kitazono, J. Kuroda, Y. Kumai, M. Kamouchi, H. Ooboshi, M. Wakisaka, T. Kawahara, K. Rokutan, S. Ibayashi, et al. NAD(P)H Oxidases in Rat Basilar Arterial Endothelial Cells Stroke, May 1, 2005; 36(5): 1040 - 1046. [Abstract] [Full Text] [PDF]
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L. Gao, W. Wang, Y.-L. Li, H. D. Schultz, D. Liu, K. G. Cornish, and I. H. Zucker Sympathoexcitation by central ANG II: Roles for AT1 receptor upregulation and NAD(P)H oxidase in RVLM Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2271 - H2279. [Abstract] [Full Text] [PDF]
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