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NAD(P)H Oxidase
Role in Cardiovascular Biology and Disease
From the Department of Medicine, Division of Cardiology, Emory University, Atlanta, Ga.
Correspondence to Kathy K. Griendling, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, 319 WMB, Atlanta, GA 30322. E-mail kgriend{at}emory.edu
Abstract—Reactive oxygen species have emerged as important molecules in cardiovascular function. Recent work has shown that NAD(P)H oxidases are major sources of superoxide in vascular cells and myocytes. The biochemical characterization, activation paradigms, structure, and function of this enzyme are now partly understood. Vascular NAD(P)H oxidases share some, but not all, characteristics of the neutrophil enzyme. In response to growth factors and cytokines, they produce superoxide, which is metabolized to hydrogen peroxide, and both of these reactive oxygen species serve as second messengers to activate multiple intracellular signaling pathways. The vascular NAD(P)H oxidases have been found to be essential in the physiological response of vascular cells, including growth, migration, and modification of the extracellular matrix. They have also been linked to hypertension and to pathological states associated with uncontrolled growth and inflammation, such as atherosclerosis.
Key Words: NAD(P)H oxidase • reactive oxygen species • superoxide • vascular cells
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A. T. Baumer, H. ten Freyhaus, H. Sauer, M. Wartenberg, K. Kappert, P. Schnabel, C. Konkol, J. Hescheler, M. Vantler, and S. Rosenkranz Phosphatidylinositol 3-Kinase-dependent Membrane Recruitment of Rac-1 and p47phox Is Critical for {alpha}-Platelet-derived Growth Factor Receptor-induced Production of Reactive Oxygen Species J. Biol. Chem., March 21, 2008; 283(12): 7864 - 7876. [Abstract] [Full Text] [PDF]
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J. M. Moreno, I. Rodriguez Gomez, R. Wangensteen, M. Alvarez-Guerra, J. d. D. Luna, J. Garcia-Estan, and F. Vargas Tempol improves renal hemodynamics and pressure natriuresis in hyperthyroid rats Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2008; 294(3): R867 - R873. [Abstract] [Full Text] [PDF]
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D. Gozal and L. Kheirandish-Gozal Cardiovascular Morbidity in Obstructive Sleep Apnea: Oxidative Stress, Inflammation, and Much More Am. J. Respir. Crit. Care Med., February 15, 2008; 177(4): 369 - 375. [Abstract] [Full Text] [PDF]
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J. C. Lee, F. Bhora, J. Sun, G. Cheng, E. Arguiri, C. C. Solomides, S. Chatterjee, and M. Christofidou-Solomidou Dietary flaxseed enhances antioxidant defenses and is protective in a mouse model of lung ischemia-reperfusion injury Am J Physiol Lung Cell Mol Physiol, February 1, 2008; 294(2): L255 - L265. [Abstract] [Full Text] [PDF]
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T. Nakamura, E. Yamamoto, K. Kataoka, T. Yamashita, Y. Tokutomi, Y.-F. Dong, S. Matsuba, H. Ogawa, and S. Kim-Mitsuyama Beneficial Effects of Pioglitazone on Hypertensive Cardiovascular Injury Are Enhanced by Combination With Candesartan Hypertension, February 1, 2008; 51(2): 296 - 301. [Abstract] [Full Text] [PDF]
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Y. H. Looi, D. J. Grieve, A. Siva, S. J. Walker, N. Anilkumar, A. C. Cave, M. Marber, M. J. Monaghan, and A. M. Shah Involvement of Nox2 NADPH Oxidase in Adverse Cardiac Remodeling After Myocardial Infarction Hypertension, February 1, 2008; 51(2): 319 - 325. [Abstract] [Full Text] [PDF]
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A. Yogi, C. Mercure, J. Touyz, G. E. Callera, A. C.I. Montezano, A. B. Aranha, R. C. Tostes, T. Reudelhuber, and R. M. Touyz Renal Redox-Sensitive Signaling, but Not Blood Pressure, Is Attenuated by Nox1 Knockout in Angiotensin II-Dependent Chronic Hypertension Hypertension, February 1, 2008; 51(2): 500 - 506. [Abstract] [Full Text] [PDF]
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S. Yagi, K.-i. Aihara, Y. Ikeda, Y. Sumitomo, S. Yoshida, T. Ise, T. Iwase, K. Ishikawa, H. Azuma, M. Akaike, et al. Pitavastatin, an HMG-CoA Reductase Inhibitor, Exerts eNOS-Independent Protective Actions Against Angiotensin II Induced Cardiovascular Remodeling and Renal Insufficiency Circ. Res., January 4, 2008; 102(1): 68 - 76. [Abstract] [Full Text] [PDF]
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Y. M. Kim, H. Kattach, C. Ratnatunga, R. Pillai, K. M. Channon, and B. Casadei Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J. Am. Coll. Cardiol., January 1, 2008; 51(1): 68 - 74. [Abstract] [Full Text] [PDF]
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J. C. Velasquez-Castano and W. R. Taylor Angiotensin II and New Vessel Formation: Aiming for the Right Oxidative Window Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 4 - 5. [Full Text] [PDF]
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F. Jiang, N. Guo, and G. J. Dusting Modulation of Nicotinamide Adenine Dinucleotide Phosphate Oxidase Expression and Function by 3',4'-Dihydroxyflavonol in Phagocytic and Vascular Cells J. Pharmacol. Exp. Ther., January 1, 2008; 324(1): 261 - 269. [Abstract] [Full Text] [PDF]
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R. Reed, C. Kolz, B. Potter, and P. Rocic The Mechanistic Basis for the Disparate Effects of Angiotensin II on Coronary Collateral Growth Arterioscler Thromb Vasc Biol, January 1, 2008; 28(1): 61 - 67. [Abstract] [Full Text] [PDF]
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A. R. Hemnes, A. Zaiman, and H. C. Champion PDE5A inhibition attenuates bleomycin-induced pulmonary fibrosis and pulmonary hypertension through inhibition of ROS generation and RhoA/Rho kinase activation Am J Physiol Lung Cell Mol Physiol, January 1, 2008; 294(1): L24 - L33. [Abstract] [Full Text] [PDF]
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S. Li, X. Li, H. Zheng, B. Xie, K. R. Bidasee, and G. J. Rozanski Pro-oxidant effect of transforming growth factor-{beta}1 mediates contractile dysfunction in rat ventricular myocytes Cardiovasc Res, January 1, 2008; 77(1): 107 - 117. [Abstract] [Full Text] [PDF]
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A. Vinh, R. E. Widdop, G. R. Drummond, and T. A. Gaspari Chronic angiotensin IV treatment reverses endothelial dysfunction in ApoE-deficient mice Cardiovasc Res, January 1, 2008; 77(1): 178 - 187. [Abstract] [Full Text] [PDF]
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A. E. Vendrov, Z. S. Hakim, N. R. Madamanchi, M. Rojas, C. Madamanchi, and M. S. Runge Atherosclerosis Is Attenuated by Limiting Superoxide Generation in Both Macrophages and Vessel Wall Cells Arterioscler Thromb Vasc Biol, December 1, 2007; 27(12): 2714 - 2721. [Abstract] [Full Text] [PDF]
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D. D. Lund, R. M. Brooks, F. M. Faraci, and D. D. Heistad Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3726 - H3731. [Abstract] [Full Text] [PDF]
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R. S. Arnold, J. He, A. Remo, D. Ritsick, Q. Yin-Goen, J. D. Lambeth, M. W. Datta, A. N. Young, and J. A. Petros Nox1 Expression Determines Cellular Reactive Oxygen and Modulates c-fos-Induced Growth Factor, Interleukin-8, and Cav-1 Am. J. Pathol., December 1, 2007; 171(6): 2021 - 2032. [Abstract] [Full Text] [PDF]
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T. Korff, K. Aufgebauer, and M. Hecker Cyclic Stretch Controls the Expression of CD40 in Endothelial Cells by Changing Their Transforming Growth Factor-{beta}1 Response Circulation, November 13, 2007; 116(20): 2288 - 2297. [Abstract] [Full Text] [PDF]
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W. Ni, Y. Zhan, H. He, E. Maynard, J. A. Balschi, and P. Oettgen Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47phox Gene Expression in Response to Angiotensin II Circ. Res., November 9, 2007; 101(10): 985 - 994. [Abstract] [Full Text] [PDF]
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K. K. Ogden, J. R. Falck, and S. W. Watts The Cytochrome P450 Inhibitor Ketoconazole Potentiates 5-Hydroxytryptamine-Induced Contraction in Rat Aorta J. Pharmacol. Exp. Ther., November 1, 2007; 323(2): 606 - 613. [Abstract] [Full Text] [PDF]
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A. Dandapat, C. Hu, L. Sun, and J. L. Mehta Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1 Dependent Redox-Sensitive Pathway Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2435 - 2442. [Abstract] [Full Text] [PDF]
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S. R. Datla, H. Peshavariya, G. J. Dusting, K. Mahadev, B. J. Goldstein, and F. Jiang Important Role of Nox4 Type NADPH Oxidase in Angiogenic Responses in Human Microvascular Endothelial Cells In Vitro Arterioscler Thromb Vasc Biol, November 1, 2007; 27(11): 2319 - 2324. [Abstract] [Full Text] [PDF]
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R. K. Upmacis, M. J. Crabtree, R. S. Deeb, H. Shen, P. B. Lane, L. E. S. Benguigui, N. Maeda, D. P. Hajjar, and S. S. Gross Profound biopterin oxidation and protein tyrosine nitration in tissues of ApoE-null mice on an atherogenic diet: contribution of inducible nitric oxide synthase Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2878 - H2887. [Abstract] [Full Text] [PDF]
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T. Hashimoto, M. Kihara, N. Imai, S.-i. Yoshida, H. Shimoyamada, H. Yasuzaki, J. Ishida, Y. Toya, Y. Kiuchi, N. Hirawa, et al. Requirement of Apelin-Apelin Receptor System for Oxidative Stress-Linked Atherosclerosis Am. J. Pathol., November 1, 2007; 171(5): 1705 - 1712. [Abstract] [Full Text] [PDF]
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