(Circulation. 1999;99:2027-2033.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Increased NADH-Oxidase–Mediated Superoxide Production in the Early Stages of Atherosclerosis
Evidence for Involvement of the Renin-Angiotensin System
From the Abteilung für Kardiologie, Universitäts-Krankenhaus Eppendorf, University of Hamburg (A.W., E.S., R.M., J.H.B., M.S., T.H., T. Meinertz, T. Münzel); the Klinik III für Innere Medizin, University of Cologne (G.N., M.B.); and Bayer Leverkusen, Wuppertal (J.P.S.), Germany; and the Division of Cardiology, Emory University, Atlanta, Ga (K.K.G., D.G.H.).
Correspondence to Thomas Münzel, MD, Abteilung für Kardiologie, Universitäts-Krankenhaus Eppendorf, Martinistraße 52, D-20246 Hamburg, Germany. E-mail muenzel{at}uke.uni-hamburg.de
Background—Angiotensin II activates NAD(P)H-dependent oxidases via AT1-receptor stimulation, the most important vascular source of superoxide (O2·-). The AT1 receptor is upregulated in vitro by low-density lipoprotein. The present study was designed to test whether hypercholesterolemia is associated with increased NAD(P)H-dependent vascular O2·- production and whether AT1-receptor blockade may inhibit this oxidase and in parallel improve endothelial dysfunction.
Methods and Results—Vascular responses were determined by isometric tension studies, and relative rates of vascular O2·- production were determined by use of chemiluminescence with lucigenin, a cypridina luciferin analogue, and electron spin resonance studies. AT1-receptor mRNA was quantified by Northern analysis, and AT1-receptor density was measured by radioligand binding assays. Hypercholesterolemia was associated with impaired endothelium-dependent vasodilation and increased O2·- production in intact vessels. In vessel homogenates, we found a significant activation of NADH-driven O2·- production in both models of hyperlipidemia. Treatment of cholesterol-fed animals with the AT1-receptor antagonist Bay 10-6734 improved endothelial dysfunction, normalized vascular O2·- and NADH-oxidase activity, decreased macrophage infiltration, and reduced early plaque formation. In the setting of hypercholesterolemia, the aortic AT1 receptor mRNA was upregulated to 166±11%, accompanied by a comparable increase in AT1-receptor density.
Conclusions—Hypercholesterolemia is associated with AT1-receptor upregulation, endothelial dysfunction, and increased NADH-dependent vascular O2·- production. The improvement of endothelial dysfunction, inhibition of the oxidase, and reduction of early plaque formation by an AT1-receptor antagonist suggests a crucial role of angiotensin II–mediated O2·- production in the early stage of atherosclerosis.
Key Words: superoxide • hypercholesterolemia • magnetic resonance spectroscopy • angiotensin
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|
|
|
|
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|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
N. R. Madamanchi, A. Vendrov, and M. S. Runge Oxidative Stress and Vascular Disease Arterioscler Thromb Vasc Biol, January 1, 2005; 25(1): 29 - 38. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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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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|
|
|
|
 |
|
 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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|
|
|
|
 |
|
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|
|
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|
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|
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|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
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|
|
|
|
|
|
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|
|
|
|
 |
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|
|
|
|
|
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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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 T. Inoguchi, T. Sonta, H. Tsubouchi, T. Etoh, M. Kakimoto, N. Sonoda, N. Sato, N. Sekiguchi, K. Kobayashi, H. Sumimoto, et al. Protein Kinase C-Dependent Increase in Reactive Oxygen Species (ROS) Production in Vascular Tissues of Diabetes: Role of Vascular NAD(P)H Oxidase J. Am. Soc. Nephrol., August 1, 2003; 14(90003): S227 - 232. [Abstract] [Full Text] [PDF]
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A. Warnholtz and T. Munzel The failing human heart: Another battlefield for the NAD(P)H oxidase? J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2172 - 2174. [Full Text] [PDF]
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B. M. Singh and J. L. Mehta Interactions Between the Renin-Angiotensin System and Dyslipidemia: Relevance in the Therapy of Hypertension and Coronary Heart Disease Arch Intern Med, June 9, 2003; 163(11): 1296 - 1304. [Abstract] [Full Text] [PDF]
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D. G Harrison, Hua Cai, U. Landmesser, and K. K Griendling The Pickering Lecture British Hypertension Society, 10th September 2002: Interactions of angiotensin II with NAD(P)H oxidase, oxidant stress and cardiovascular disease Journal of Renin-Angiotensin-Aldosterone System, June 1, 2003; 4(2): 51 - 61. [Abstract] [PDF]
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J. Galle, A. Mameghani, S.-S. Bolz, S. Gambaryan, M. Gorg, T. Quaschning, U. Raff, H. Barth, S. Seibold, C. Wanner, et al. Oxidized LDL and its Compound Lysophosphatidylcholine Potentiate AngII-Induced Vasoconstriction by Stimulation of RhoA J. Am. Soc. Nephrol., June 1, 2003; 14(6): 1471 - 1479. [Abstract] [Full Text] [PDF]
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T. Matsumoto, K. Minai, H. Horie, N. Ohira, H. Takashima, Y. Tarutani, Y. o Yasuda, T. Ozawa, S. Matsuo, M. Kinoshita, et al. Angiotensin-converting enzyme inhibition but not angiotensin II type 1 receptor antagonism augments coronary release of tissue plasminogen activator in hypertensive patients J. Am. Coll. Cardiol., April 16, 2003; 41(8): 1373 - 1379. [Abstract] [Full Text] [PDF]
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S. Spiekermann, U. Landmesser, S. Dikalov, M. Bredt, G. Gamez, H. Tatge, N. Reepschlager, B. Hornig, H. Drexler, and D. G. Harrison Electron Spin Resonance Characterization of Vascular Xanthine and NAD(P)H Oxidase Activity in Patients With Coronary Artery Disease: Relation to Endothelium-Dependent Vasodilation Circulation, March 18, 2003; 107(10): 1383 - 1389. [Abstract] [Full Text] [PDF]
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P. A. Fischer, G. N. Dominguez, L. A. Cuniberti, V. Martinez, J. P. Werba, A. J. Ramirez, and L. D. Masnatta Hyperhomocysteinemia Induces Renal Hemodynamic Dysfunction: Is Nitric Oxide Involved? J. Am. Soc. Nephrol., March 1, 2003; 14(3): 653 - 660. [Abstract] [Full Text] [PDF]
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H.-Y. Sohn, F. Krotz, S. Zahler, T. Gloe, M. Keller, K. Theisen, T. M Schiele, V. Klauss, and U. Pohl Crucial role of local peroxynitrite formation in neutrophil-induced endothelial cell activation Cardiovasc Res, March 1, 2003; 57(3): 804 - 815. [Abstract] [Full Text] [PDF]
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T. J. Anderson, J. Hubacek, D. G. Wyse, and M. L. Knudtson Effect of chelation therapy on endothelial function in patients with coronary artery disease: PATCH substudy J. Am. Coll. Cardiol., February 5, 2003; 41(3): 420 - 425. [Abstract] [Full Text] [PDF]
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 U. Landmesser and H. Drexler Oxidative stress, the renin-angiotensin system, and atherosclerosis Eur. Heart J. Suppl., January 1, 2003; 5(suppl_A): A3 - A7. [Abstract] [PDF]
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 H. Cai, Z. Li, S. Dikalov, S. M. Holland, J. Hwang, H. Jo, S. C. Dudley Jr., and D. G. Harrison NAD(P)H Oxidase-derived Hydrogen Peroxide Mediates Endothelial Nitric Oxide Production in Response to Angiotensin II J. Biol. Chem., December 6, 2002; 277(50): 48311 - 48317. [Abstract] [Full Text] [PDF]
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P. T. Schumacker Angiotensin II Signaling in the Brain: Compartmentalization of Redox Signaling? Circ. Res., November 29, 2002; 91(11): 982 - 984. [Full Text] [PDF]
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 J. S. Forrester Prevention of Plaque Rupture: A New Paradigm of Therapy Ann Intern Med, November 19, 2002; 137(10): 823 - 833. [Abstract] [Full Text] [PDF]
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S. Klahr and J. Morrissey Obstructive nephropathy and renal fibrosis Am J Physiol Renal Physiol, November 1, 2002; 283(5): F861 - F875. [Abstract] [Full Text] [PDF]
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U. Rueckschloss, M. T. Quinn, J. Holtz, and H. Morawietz Dose-Dependent Regulation of NAD(P)H Oxidase Expression by Angiotensin II in Human Endothelial Cells: Protective Effect of Angiotensin II Type 1 Receptor Blockade in Patients With Coronary Artery Disease Arterioscler Thromb Vasc Biol, November 1, 2002; 22(11): 1845 - 1851. [Abstract] [Full Text] [PDF]
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C. A. Hamilton, M. J. Brosnan, S. Al-Benna, G. Berg, and A. F. Dominiczak NAD(P)H Oxidase Inhibition Improves Endothelial Function in Rat and Human Blood Vessels Hypertension, November 1, 2002; 40(5): 755 - 762. [Abstract] [Full Text] [PDF]
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T. Gori and J. D. Parker The Puzzle of Nitrate Tolerance: Pieces Smaller Than We Thought? Circulation, October 29, 2002; 106(18): 2404 - 2408. [Full Text] [PDF]
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A. Warnholtz, H. Mollnau, T. Heitzer, A. Kontush, T. Moller-Bertram, D. Lavall, A. Giaid, U. Beisiegel, S. L. Marklund, U. Walter, et al. Adverse effects of nitroglycerin treatment on endothelial function, vascular nitrotyrosine levels and cGMP-dependent protein kinase activity in hyperlipidemic Watanabe rabbits J. Am. Coll. Cardiol., October 2, 2002; 40(7): 1356 - 1363. [Abstract] [Full Text] [PDF]
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A. Virdis, M. F. Neves, F. Amiri, E. Viel, R. M. Touyz, and E. L. Schiffrin Spironolactone Improves Angiotensin-Induced Vascular Changes and Oxidative Stress Hypertension, October 1, 2002; 40(4): 504 - 510. [Abstract] [Full Text] [PDF]
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U. Landmesser, H. Cai, S. Dikalov, L. McCann, J. Hwang, H. Jo, S. M. Holland, and D. G. Harrison Role of p47phox in Vascular Oxidative Stress and Hypertension Caused by Angiotensin II Hypertension, October 1, 2002; 40(4): 511 - 515. [Abstract] [Full Text] [PDF]
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A. R. Brasier, A. Recinos III, and M. S. Eledrisi Vascular Inflammation and the Renin-Angiotensin System Arterioscler Thromb Vasc Biol, August 1, 2002; 22(8): 1257 - 1266. [Abstract] [Full Text] [PDF]
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T. M. Paravicini, L. M. Gulluyan, G. J. Dusting, and G. R. Drummond Increased NADPH Oxidase Activity, gp91phox Expression, and Endothelium-Dependent Vasorelaxation During Neointima Formation in Rabbits Circ. Res., July 12, 2002; 91(1): 54 - 61. [Abstract] [Full Text] [PDF]
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S. Wassmann, S. Hilgers, U. Laufs, M. Bohm, and G. Nickenig Angiotensin II Type 1 Receptor Antagonism Improves Hypercholesterolemia-Associated Endothelial Dysfunction Arterioscler Thromb Vasc Biol, July 1, 2002; 22(7): 1208 - 1212. [Abstract] [Full Text] [PDF]
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A. H Chester Mast cells feel the strain Cardiovasc Res, July 1, 2002; 55(1): 13 - 15. [Full Text] [PDF]
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S. Itoh, S. Umemoto, M. Hiromoto, Y. Toma, Y. Tomochika, S. Aoyagi, M. Tanaka, T. Fujii, and M. Matsuzaki Importance of NAD(P)H Oxidase-Mediated Oxidative Stress and Contractile Type Smooth Muscle Myosin Heavy Chain SM2 at the Early Stage of Atherosclerosis Circulation, May 14, 2002; 105(19): 2288 - 2295. [Abstract] [Full Text] [PDF]
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J. Herrmann, P. J. Best, E. L. Ritman, D. R. Holmes Jr, L. O. Lerman, and A. Lerman Chronic endothelin receptor antagonism prevents coronary vasa vasorum neovascularization in experimental hypercholesterolemia J. Am. Coll. Cardiol., May 1, 2002; 39(9): 1555 - 1561. [Abstract] [Full Text] [PDF]
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S. Keidar, R. Heinrich, M. Kaplan, and M. Aviram Oxidative stress increases the expression of the angiotensin-II receptor type 1 in mouse peritoneal macrophages Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1): 24 - 30. [Abstract] [PDF]
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B.-q. Zhu, R. E Sievers, A. E. Browne, R. T Hillman, K. Chair, R. J Lee, K. Chatterjee, S. A Glantz, and W. W Parmley The renin-angiotensin system does not contribute to the endothelial dysfunction and increased infarct size in rats exposed to second hand smoke Journal of Renin-Angiotensin-Aldosterone System, March 1, 2002; 3(1): 54 - 60. [Abstract] [PDF]
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