© 1999 American Heart Association, Inc.
Review |
Oxidative Stress as a Regulator of Gene Expression in the Vasculature
From AtheroGenics, Inc (C.K., R.M.M.), Alpharetta, and Division of Cardiology (R.M.M.), Department of Medicine, Emory University School of Medicine, Atlanta, Ga.
Correspondence to Russell M. Medford, MD, PhD, AtheroGenics, Inc, 8995 Westside Pkwy, Alpharetta, GA 30004. E-mail rmedford{at}atherogen.com
Abstract—Oxidative stress and the production of intracellular reactive oxygen species (ROS) have been implicated in the pathogenesis of a variety of diseases. In excess, ROS and their byproducts that are capable of causing oxidative damage may be cytotoxic to cells. However, it is now well established that moderate amounts of ROS play a role in signal transduction processes such as cell growth and posttranslational modification of proteins. Oxidants, antioxidants, and other determinants of the intracellular reduction-oxidation (redox) state play an important role in the regulation of gene expression. Recent insights into the etiology and pathogenesis of atherosclerosis suggest that this disease may be viewed as an inflammatory disease linked to an abnormality in oxidation-mediated signals in the vasculature. In this review, we summarize the evidence supporting the notion that oxidative stress and the production of ROS function as physiological regulators of vascular gene expression mediated via specific redox-sensitive signal transduction pathways and transcriptional regulatory networks. Elucidating, at the molecular level, the regulatory processes involved in redox-sensitive vascular gene expression represents a foundation not only for understanding the pathogenesis of atherosclerosis and other inflammatory diseases but also for the development of novel therapeutic treatment strategies.
Key Words: redox • gene expression • atherosclerosis • oxidation • signaling
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A. V. Chobanian, G. L. Bakris, H. R. Black, W. C. Cushman, L. A. Green, J. L. Izzo Jr, D. W. Jones, B. J. Materson, S. Oparil, J. T. Wright Jr, et al. Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure Hypertension, December 1, 2003; 42(6): 1206 - 1252. [Abstract] [Full Text] [PDF]
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K. K. Griendling and G. A. FitzGerald Oxidative Stress and Cardiovascular Injury: Part I: Basic Mechanisms and In Vivo Monitoring of ROS Circulation, October 21, 2003; 108(16): 1912 - 1916. [Full Text] [PDF]
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D. B. Cowan, M. Jones, L. M. Garcia, S. Noria, P. J. del Nido, and F. X. McGowan Jr Hypoxia and Stretch Regulate Intercellular Communication in Vascular Smooth Muscle Cells Through Reactive Oxygen Species Formation Arterioscler. Thromb. Vasc. Biol., October 1, 2003; 23(10): 1754 - 1760. [Abstract] [Full Text] [PDF]
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T. Aizawa, H. Wei, J. M. Miano, J.-i. Abe, B. C. Berk, and C. Yan Role of Phosphodiesterase 3 in NO/cGMP-Mediated Antiinflammatory Effects in Vascular Smooth Muscle Cells Circ. Res., September 5, 2003; 93(5): 406 - 413. [Abstract] [Full Text] [PDF]
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B. Lassegue and R. E. Clempus Vascular NAD(P)H oxidases: specific features, expression, and regulation Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2003; 285(2): R277 - R297. [Abstract] [Full Text] [PDF]
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C. L. Sundell, P. K. Somers, C. Q. Meng, L. K. Hoong, K.-L. Suen, R. R. Hill, L. K. Landers, A. Chapman, D. Butteiger, M. Jones, et al. AGI-1067: A Multifunctional Phenolic Antioxidant, Lipid Modulator, Anti-Inflammatory and Antiatherosclerotic Agent J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 1116 - 1123. [Abstract] [Full Text] [PDF]
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G. Basta, L. Venneri, G. Lazzerini, E. Pasanisi, M. Pianelli, N. Vesentini, S. Del Turco, C. Kusmic, and E. Picano In vitro modulation of intracellular oxidative stress of endothelial cells by diagnostic cardiac ultrasound Cardiovasc Res, April 1, 2003; 58(1): 156 - 161. [Abstract] [Full Text] [PDF]
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R. Dechend, C. Viedt, D. N. Muller, B. Ugele, R. P. Brandes, G. Wallukat, J.-K. Park, J. Janke, P. Barta, J. Theuer, et al. AT1 Receptor Agonistic Antibodies From Preeclamptic Patients Stimulate NADPH Oxidase Circulation, April 1, 2003; 107(12): 1632 - 1639. [Abstract] [Full Text] [PDF]
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H. F. Lopes, K. L. Martin, K. Nashar, J. D. Morrow, T. L. Goodfriend, and B. M. Egan DASH Diet Lowers Blood Pressure and Lipid-Induced Oxidative Stress in Obesity Hypertension, March 1, 2003; 41(3): 422 - 430. [Abstract] [Full Text] [PDF]
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J.-C. Tardif, J. Gregoire, L. Schwartz, L. Title, L. Laramee, F. Reeves, J. Lesperance, M. G. Bourassa, P. L. L'Allier, M. Glass, et al. Effects of AGI-1067 and Probucol After Percutaneous Coronary Interventions Circulation, February 4, 2003; 107(4): 552 - 558. [Abstract] [Full Text] [PDF]
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M. Iglarz, R. M. Touyz, F. Amiri, M.-F. Lavoie, Q. N. Diep, and E. L. Schiffrin Effect of Peroxisome Proliferator-Activated Receptor-{alpha} and -{gamma} Activators on Vascular Remodeling in Endothelin-Dependent Hypertension Arterioscler. Thromb. Vasc. Biol., January 1, 2003; 23(1): 45 - 51. [Abstract] [Full Text] [PDF]
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R. W. Alexander Oxidized LDL Autoantibodies, Endothelial Dysfunction, and Transplant-Associated Arteriosclerosis Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 1950 - 1951. [Full Text] [PDF]
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T. K. Nakahashi, K. Hoshina, P. S. Tsao, E. Sho, M. Sho, J. K. Karwowski, C. Yeh, R.-B. Yang, J. N. Topper, and R. L. Dalman Flow Loading Induces Macrophage Antioxidative Gene Expression in Experimental Aneurysms Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2017 - 2022. [Abstract] [Full Text] [PDF]
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J. C. Fang, S. Kinlay, D. Behrendt, H. Hikita, J. L. Witztum, A. P. Selwyn, and P. Ganz Circulating Autoantibodies to Oxidized LDL Correlate With Impaired Coronary Endothelial Function After Cardiac Transplantation Arterioscler. Thromb. Vasc. Biol., December 1, 2002; 22(12): 2044 - 2048. [Abstract] [Full Text] [PDF]
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J.-M. Li, N. P. Gall, D. J. Grieve, M. Chen, and A. M. Shah Activation of NADPH Oxidase During Progression of Cardiac Hypertrophy to Failure Hypertension, October 1, 2002; 40(4): 477 - 484. [Abstract] [Full Text] [PDF]
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W. Martinet, M. W.M. Knaapen, G. R.Y. De Meyer, A. G. Herman, and M. M. Kockx Elevated Levels of Oxidative DNA Damage and DNA Repair Enzymes in Human Atherosclerotic Plaques Circulation, August 20, 2002; 106(8): 927 - 932. [Abstract] [Full Text] [PDF]
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M. T Gewaltig and G. Kojda Vasoprotection by nitric oxide: mechanisms and therapeutic potential Cardiovasc Res, August 1, 2002; 55(2): 250 - 260. [Abstract] [Full Text] [PDF]
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G. NICKENIG, S. BAUDLER, C. MULLER, C. WERNER, N. WERNER, H. WELZEL, K. STREHLOW, and M. BOHM Redox-sensitive vascular smooth muscle cell proliferation is mediated by GKLF and Id3 in vitro and in vivo FASEB J, July 1, 2002; 16(9): 1077 - 1086. [Abstract] [Full Text] [PDF]
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H. Fan, B. Sun, Q. Gu, A. Lafond-Walker, S. Cao, and L. C. Becker Oxygen radicals trigger activation of NF-kappa B and AP-1 and upregulation of ICAM-1 in reperfused canine heart Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1778 - H1786. [Abstract] [Full Text] [PDF]
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C. Kumaran and K. Shivakumar Calcium- and superoxide anion-mediated mitogenic action of substance P on cardiac fibroblasts Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1855 - H1862. [Abstract] [Full Text] [PDF]
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T. Ide, H. Tsutsui, N. Ohashi, S. Hayashidani, N. Suematsu, M. Tsuchihashi, H. Tamai, and A. Takeshita Greater Oxidative Stress in Healthy Young Men Compared With Premenopausal Women Arterioscler. Thromb. Vasc. Biol., March 1, 2002; 22(3): 438 - 442. [Abstract] [Full Text] [PDF]
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M. Rodriguez-Porcel, L. O Lerman, D. R Holmes Jr., D. Richardson, C. Napoli, and A. Lerman Chronic antioxidant supplementation attenuates nuclear factor-{kappa}B activation and preserves endothelial function in hypercholesterolemic pigs Cardiovasc Res, March 1, 2002; 53(4): 1010 - 1018. [Abstract] [Full Text] [PDF]
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J.-M. Li, A. M. Mullen, S. Yun, F. Wientjes, G. Y. Brouns, A. J. Thrasher, and A. M. Shah Essential Role of the NADPH Oxidase Subunit p47phox in Endothelial Cell Superoxide Production in Response to Phorbol Ester and Tumor Necrosis Factor-{alpha} Circ. Res., February 8, 2002; 90(2): 143 - 150. [Abstract] [Full Text] [PDF]
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