This Article Full Text Full Text (PDF) All Versions of this Article: 44/4/381    most recent 01.HYP.0000142232.29764.a7v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wassmann, S. Articles by Nickenig, G. Search for Related Content PubMed PubMed Citation Articles by Wassmann, S. Articles by Nickenig, G. Related Collections Other hypertension Mechanism of atherosclerosis/growth factors Animal models of human disease Pathophysiology Cell signalling/signal transduction Gene expression Hypertension - basic studies

(Hypertension. 2004;44:381.)
© 2004 American Heart Association, Inc.

Brief Reviews

Modulation of Oxidant and Antioxidant Enzyme Expression and Function in Vascular Cells

From Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar, Germany.

Correspondence to Prof. Georg Nickenig, Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, D-66421 Homburg/Saar, Germany. E-mail nickenig{at}med-in.uni-sb.de

Pathological conditions that predispose to cardiovascular events, such as hypertension, hypercholesterolemia, and diabetes, are associated with oxidative stress. These observations and further data derived from a plethora of investigations provided accumulating evidence that oxidative stress is decisively involved in the pathogenesis of endothelial dysfunction and atherosclerosis. Several enzymes expressed in vascular tissue contribute to production and efficient degradation of reactive oxygen species, and enhanced activity of oxidant enzymes and/or reduced activity of antioxidant enzymes may cause oxidative stress. Various agonists, pathological conditions, and therapeutic interventions lead to modulated expression and function of oxidant and antioxidant enzymes, including NAD(P)H oxidase, endothelial nitric oxide synthase, xanthine oxidase, myeloperoxidase, superoxide dismutases, catalase, thioredoxin reductase, and glutathione peroxidase. Data from numerous studies underline the importance of dysregulated oxidant and antioxidant enzymes for the development and progression of atherosclerotic disease in animal models and humans. Specific pharmacological modulation of key enzymes involved in the propagation of oxidative stress rather than using direct antioxidants may be an approach to reduce oxygen radical load in the vasculature and subsequent disease progression in humans. This review focuses on the modulation of expression and activity of major antioxidant and oxidant enzymes expressed in vascular cells.

Key Words: free radicals • oxidative stress • enzymes • gene regulation • atherosclerosis

This article has been cited by other articles:

				Y. Fan, Y. Wang, Z. Tang, H. Zhang, X. Qin, Y. Zhu, Y. Guan, X. Wang, B. Staels, S. Chien, et al. Suppression of Pro-inflammatory Adhesion Molecules by PPAR-{delta} in Human Vascular Endothelial Cells Arterioscler. Thromb. Vasc. Biol., February 1, 2008; 28(2): 315 - 321. [Abstract] [Full Text] [PDF]

				T. M. Paravicini and R. M. Touyz NADPH Oxidases, Reactive Oxygen Species, and Hypertension: Clinical implications and therapeutic possibilities Diabetes Care, February 1, 2008; 31(Supplement_2): S170 - S180. [Abstract] [Full Text] [PDF]

				C. Wadham, A. Parker, L. Wang, and P. Xia High Glucose Attenuates Protein S-Nitrosylation in Endothelial Cells: Role of Oxidative Stress Diabetes, November 1, 2007; 56(11): 2715 - 2721. [Abstract] [Full Text] [PDF]

				C. L. Sartorio, D. Fraccarollo, P. Galuppo, M. Leutke, G. Ertl, I. Stefanon, and J. Bauersachs Mineralocorticoid Receptor Blockade Improves Vasomotor Dysfunction and Vascular Oxidative Stress Early After Myocardial Infarction Hypertension, November 1, 2007; 50(5): 919 - 925. [Abstract] [Full Text] [PDF]

				S. Sharma, A. C. Grobe, D. A. Wiseman, S. Kumar, M. Englaish, I. Najwer, E. Benavidez, P. Oishi, A. Azakie, J. R. Fineman, et al. Lung antioxidant enzymes are regulated by development and increased pulmonary blood flow Am J Physiol Lung Cell Mol Physiol, October 1, 2007; 293(4): L960 - L971. [Abstract] [Full Text] [PDF]

				P. Lewis, N. Stefanovic, J. Pete, A. C. Calkin, S. Giunti, V. Thallas-Bonke, K. A. Jandeleit-Dahm, T. J. Allen, I. Kola, M. E. Cooper, et al. Lack of the Antioxidant Enzyme Glutathione Peroxidase-1 Accelerates Atherosclerosis in Diabetic Apolipoprotein E-Deficient Mice Circulation, April 24, 2007; 115(16): 2178 - 2187. [Abstract] [Full Text] [PDF]

				A. Shamaei-Tousi, J. P. Halcox, and B. Henderson Stressing the obvious? Cell stress and cell stress proteins in cardiovascular disease Cardiovasc Res, April 1, 2007; 74(1): 19 - 28. [Abstract] [Full Text] [PDF]

				J. L. Figarola, N. Shanmugam, R. Natarajan, and S. Rahbar Anti-Inflammatory Effects of the Advanced Glycation End Product Inhibitor LR-90 in Human Monocytes Diabetes, March 1, 2007; 56(3): 647 - 655. [Abstract] [Full Text] [PDF]

				T. Szasz, K. Thakali, G. D. Fink, and S. W. Watts A Comparison of Arteries and Veins in Oxidative Stress: Producers, Destroyers, Function, and Disease Experimental Biology and Medicine, January 1, 2007; 232(1): 27 - 37. [Abstract] [Full Text] [PDF]

				A. Schafer, C. Schulz, D. Fraccarollo, P. Tas, M. Leutke, M. Eigenthaler, S. Seidl, P. Heider, G. Ertl, S. Massberg, et al. The CX3C Chemokine Fractalkine Induces Vascular Dysfunction by Generation of Superoxide Anions Arterioscler. Thromb. Vasc. Biol., January 1, 2007; 27(1): 55 - 62. [Abstract] [Full Text] [PDF]

				M. Li, J.-F. Chiu, B. T. Mossman, and N. K. Fukagawa Down-regulation of Manganese-Superoxide Dismutase through Phosphorylation of FOXO3a by Akt in Explanted Vascular Smooth Muscle Cells from Old Rats J. Biol. Chem., December 29, 2006; 281(52): 40429 - 40439. [Abstract] [Full Text] [PDF]

				M. Mahmoudi, J. Mercer, and M. Bennett DNA damage and repair in atherosclerosis Cardiovasc Res, July 15, 2006; 71(2): 259 - 268. [Abstract] [Full Text] [PDF]

				A. C. Grobe, S. M. Wells, E. Benavidez, P. Oishi, A. Azakie, J. R. Fineman, and S. M. Black Increased oxidative stress in lambs with increased pulmonary blood flow and pulmonary hypertension: role of NADPH oxidase and endothelial NO synthase Am J Physiol Lung Cell Mol Physiol, June 1, 2006; 290(6): L1069 - L1077. [Abstract] [Full Text] [PDF]

				G. Galasso, S. Schiekofer, K. Sato, R. Shibata, D. E. Handy, N. Ouchi, J. A. Leopold, J. Loscalzo, and K. Walsh Impaired Angiogenesis in Glutathione Peroxidase-1-Deficient Mice Is Associated With Endothelial Progenitor Cell Dysfunction Circ. Res., February 3, 2006; 98(2): 254 - 261. [Abstract] [Full Text] [PDF]

				H. A. Seow, P. G. Penketh, K. Shyam, S. Rockwell, and A. C. Sartorelli PNAS, June 28, 2005; 102(26): 9282 - 9287. [Abstract] [Full Text] [PDF]

				R. Schnabel, K. J. Lackner, H. J. Rupprecht, C. Espinola-Klein, M. Torzewski, E. Lubos, C. Bickel, F. Cambien, L. Tiret, T. Munzel, et al. Glutathione Peroxidase-1 and Homocysteine for Cardiovascular Risk Prediction: Results from the AtheroGene Study J. Am. Coll. Cardiol., May 17, 2005; 45(10): 1631 - 1637. [Abstract] [Full Text] [PDF]

				K. Y Stokes and D. N. Granger The microcirculation: a motor for the systemic inflammatory response and large vessel disease induced by hypercholesterolaemia? J. Physiol., February 1, 2005; 562(3): 647 - 653. [Abstract] [Full Text] [PDF]