Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:2175-2183
© 2000 American Heart Association, Inc.
Brief Review |
Modulation of Protein Kinase Activity and Gene Expression by Reactive Oxygen Species and Their Role in Vascular Physiology and Pathophysiology
From the Division of Cardiology, Emory University, Atlanta, Ga.
Correspondence to Kathy K. Griendling, PhD, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, 319 WMB, Atlanta, GA 30322. E-mail kgriend{at}emory.edu
Abstract—Emerging evidence indicates that reactive oxygen species, especially superoxide and hydrogen peroxide, are important signaling molecules in cardiovascular cells. Their production is regulated by hormone-sensitive enzymes such as the vascular NAD(P)H oxidases, and their metabolism is coordinated by antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Both of these reactive oxygen species serve as second messengers to activate multiple intracellular proteins and enzymes, including the epidermal growth factor receptor, c-Src, p38 mitogen-activated protein kinase, Ras, and Akt/protein kinase B. Activation of these signaling cascades and redox-sensitive transcription factors leads to induction of many genes with important functional roles in the physiology and pathophysiology of vascular cells. Thus, reactive oxygen species participate in vascular smooth muscle cell growth and migration; modulation of endothelial function, including endothelium-dependent relaxation and expression of a proinflammatory phenotype; and modification of the extracellular matrix. All of these events play important roles in vascular diseases such as hypertension and atherosclerosis, suggesting that the sources of reactive oxygen species and the signaling pathways that they modify may represent important therapeutic targets.
Key Words: reactive oxygen species • vascular smooth muscle • endothelial cells • hypertension • atherosclerosis
This article has been cited by other articles:
 |
|
 |
|
  G. A. Knock, V. A. Snetkov, Y. Shaifta, S. Drndarski, J. P.T. Ward, and P. I. Aaronson Role of src-family kinases in hypoxic vasoconstriction of rat pulmonary artery Cardiovasc Res, August 23, 2008; (2008) cvn209v2. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Liu, L. Gao, S. K. Roy, K. G. Cornish, and I. H. Zucker Role of Oxidant Stress on AT1 Receptor Expression in Neurons of Rabbits With Heart Failure and in Cultured Neurons Circ. Res., July 18, 2008; 103(2): 186 - 193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Haurani, M. E. Cifuentes, A. D. Shepard, and P. J. Pagano Nox4 Oxidase Overexpression Specifically Decreases Endogenous Nox4 mRNA and Inhibits Angiotensin II-Induced Adventitial Myofibroblast Migration Hypertension, July 1, 2008; 52(1): 143 - 149. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Mollace, S. Ragusa, I. Sacco, C. Muscoli, F. Sculco, V. Visalli, E. Palma, S. Muscoli, L. Mondello, P. Dugo, et al. The Protective Effect of Bergamot Oil Extract on Lecitine-like OxyLDL Receptor-1 Expression in Balloon Injury-related Neointima Formation Journal of Cardiovascular Pharmacology and Therapeutics, June 1, 2008; 13(2): 120 - 129. [Abstract] [PDF]
|
|
|
|
 |
|
 N. Sud, S. M. Wells, S. Sharma, D. A. Wiseman, J. Wilham, and S. M. Black Asymmetric dimethylarginine inhibits HSP90 activity in pulmonary arterial endothelial cells: role of mitochondrial dysfunction Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1407 - C1418. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. G. DeMarco, J. Habibi, A. T. Whaley-Connell, R. I. Schneider, R. L. Heller, J. P. Bosanquet, M. R. Hayden, K. Delcour, S. A. Cooper, B. T. Andresen, et al. Oxidative stress contributes to pulmonary hypertension in the transgenic (mRen2)27 rat Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2659 - H2668. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Takahashi, E. Suzuki, R. Takeda, S. Oba, H. Nishimatsu, K. Kimura, T. Nagano, R. Nagai, and Y. Hirata Angiotensin II and tumor necrosis factor-{alpha} synergistically promote monocyte chemoattractant protein-1 expression: roles of NF-{kappa}B, p38, and reactive oxygen species Am J Physiol Heart Circ Physiol, June 1, 2008; 294(6): H2879 - H2888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. E. Herbert, Y. Mistry, R. Hastings, T. Poolman, L. Niklason, and B. Williams Angiotensin II-Mediated Oxidative DNA Damage Accelerates Cellular Senescence in Cultured Human Vascular Smooth Muscle Cells via Telomere-Dependent and Independent Pathways Circ. Res., February 1, 2008; 102(2): 201 - 208. [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]
|
|
|
|
 |
|
 H. Choi, T. L. Leto, L. Hunyady, K. J. Catt, Y. S. Bae, and S. G. Rhee Mechanism of Angiotensin II-induced Superoxide Production in Cells Reconstituted with Angiotensin Type 1 Receptor and the Components of NADPH Oxidase J. Biol. Chem., January 4, 2008; 283(1): 255 - 267. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. W.T. Liu and P. L. Huang Cardiovascular roles of nitric oxide: A review of insights from nitric oxide synthase gene disrupted mice Cardiovasc Res, January 1, 2008; 77(1): 19 - 29. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Erusalimsky and S. Moncada Nitric Oxide and Mitochondrial Signaling: From Physiology to Pathophysiology Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2524 - 2531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L.-J. Min, M. Mogi, J. Iwanami, J.-M. Li, A. Sakata, T. Fujita, K. Tsukuda, M. Iwai, and M. Horiuchi Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence Cardiovasc Res, December 1, 2007; 76(3): 506 - 516. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Adachi, M. Yamamoto, and M. Suematsu Targeting NAD(P)H Oxidase: Ets-1 Regulates p47phox Circ. Res., November 9, 2007; 101(10): 962 - 964. [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
M. J. Haurani and P. J. Pagano Adventitial fibroblast reactive oxygen species as autacrine and paracrine mediators of remodeling: Bellwether for vascular disease? Cardiovasc Res, September 1, 2007; 75(4): 679 - 689. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. Luyendyk, J. D. Piper, M. Tencati, K. V. Reddy, T. Holscher, R. Zhang, J. Luchoomun, X. Chen, W. Min, C. Kunsch, et al. A Novel Class of Antioxidants Inhibit LPS Induction of Tissue Factor by Selective Inhibition of the Activation of ASK1 and MAP Kinases Arterioscler. Thromb. Vasc. Biol., August 1, 2007; 27(8): 1857 - 1863. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Pirillo, P. Uboldi, G. Pappalardo, H. Kuhn, and A. L. Catapano Modification of HDL3 by mild oxidative stress increases ATP-binding cassette transporter 1-mediated cholesterol efflux Cardiovasc Res, August 1, 2007; 75(3): 566 - 574. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kitayama, F. M. Faraci, S. R. Lentz, and D. D. Heistad Cerebral Vascular Dysfunction During Hypercholesterolemia Stroke, July 1, 2007; 38(7): 2136 - 2141. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. S. Barbieri and B. B. Weksler Tobacco smoke cooperates with interleukin-1{beta} to alter {beta}-catenin trafficking in vascular endothelium resulting in increased permeability and induction of cyclooxygenase-2 expression in vitro and in vivo FASEB J, June 1, 2007; 21(8): 1831 - 1843. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Ding, A. Chapman, R. Boyd, and H. D. Wang ERK activation contributes to regulation of spontaneous contractile tone via superoxide anion in isolated rat aorta of angiotensin II-induced hypertension Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H2997 - H3005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yusof, K. Kamada, F. Spencer Gaskin, and R. J. Korthuis Angiotensin II mediates postischemic leukocyte-endothelial interactions: role of calcitonin gene-related peptide Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3032 - H3037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Larghero, R. Vene, S. Minghelli, G. Travaini, M. Morini, N. Ferrari, U. Pfeffer, D. M. Noonan, A. Albini, and R. Benelli Biological assays and genomic analysis reveal lipoic acid modulation of endothelial cell behavior and gene expression Carcinogenesis, May 1, 2007; 28(5): 1008 - 1020. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. N. Mayorov Brain superoxide as a key regulator of the cardiovascular response to emotional stress in rabbits Exp Physiol, May 1, 2007; 92(3): 471 - 479. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Alcaraz, D. Iyu, N. M. Atucha, J. Garcia-Estan, and M. C. Ortiz Vitamin E supplementation reverses renal altered vascular reactivity in chronic bile duct-ligated rats Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2007; 292(4): R1486 - R1493. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Liu, T. Shimosawa, H. Matsui, F. Meng, S. C. Supowit, D. J. DiPette, K. Ando, and T. Fujita Adrenomedullin inhibits angiotensin II-induced oxidative stress via Csk-mediated inhibition of Src activity Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1714 - H1721. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Chakraborty, H. Brooks, P. Zhang, W. Smith, M. R. McReynolds, J. B. Hoying, R. Bick, L. Truong, B. Poindexter, H. Lan, et al. Stanniocalcin-1 regulates endothelial gene expression and modulates transendothelial migration of leukocytes Am J Physiol Renal Physiol, February 1, 2007; 292(2): F895 - F904. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Bedard and K.-H. Krause The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology Physiol Rev, January 1, 2007; 87(1): 245 - 313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Thakali, L. Davenport, G. D. Fink, and S. W. Watts Cyclooxygenase, p38 Mitogen-Activated Protein Kinase (MAPK), Extracellular Signal-Regulated Kinase MAPK, Rho Kinase, and Src Mediate Hydrogen Peroxide-Induced Contraction of Rat Thoracic Aorta and Vena Cava J. Pharmacol. Exp. Ther., January 1, 2007; 320(1): 236 - 243. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Orosz, A. Csiszar, N. Labinskyy, K. Smith, P. M. Kaminski, P. Ferdinandy, M. S. Wolin, A. Rivera, and Z. Ungvari Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H130 - H139. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-Y. Lin, Y.-H. Chen, Y.-W. Lin, J.-S. Tsai, J.-W. Chen, H.-J. Wang, Y.-L. Chen, C.-Y. Li, and S.-J. Lin The Role of Human Antigen R, an RNA-binding Protein, in Mediating the Stabilization of Toll-Like Receptor 4 mRNA Induced by Endotoxin: A Novel Mechanism Involved in Vascular Inflammation Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2622 - 2629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F.-Y. Lin, Y.-H. Chen, J.-S. Tasi, J.-W. Chen, T.-L. Yang, H.-J. Wang, C.-Y. Li, Y.-L. Chen, and S.-J. Lin Endotoxin Induces Toll-Like Receptor 4 Expression in Vascular Smooth Muscle Cells via NADPH Oxidase Activation and Mitogen-Activated Protein Kinase Signaling Pathways Arterioscler. Thromb. Vasc. Biol., December 1, 2006; 26(12): 2630 - 2637. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ushio-Fukai and R. W. Alexander Caveolin-Dependent Angiotensin II Type 1 Receptor Signaling in Vascular Smooth Muscle Hypertension, November 1, 2006; 48(5): 797 - 803. [Full Text] [PDF]
|
|
|
|
|
|
C. E. Murdoch, M. Zhang, A. C. Cave, and A. M. Shah NADPH oxidase-dependent redox signalling in cardiac hypertrophy, remodelling and failure Cardiovasc Res, July 15, 2006; 71(2): 208 - 215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. E. Clempus and K. K. Griendling Reactive oxygen species signaling in vascular smooth muscle cells Cardiovasc Res, July 15, 2006; 71(2): 216 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. M. Paravicini and R. M. Touyz Redox signaling in hypertension Cardiovasc Res, July 15, 2006; 71(2): 247 - 258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. V. Ramana, A. Bhatnagar, S. Srivastava, U. C. Yadav, S. Awasthi, Y. C. Awasthi, and S. K. Srivastava Mitogenic Responses of Vascular Smooth Muscle Cells to Lipid Peroxidation-derived Aldehyde 4-Hydroxy-trans-2-nonenal (HNE): ROLE OF ALDOSE REDUCTASE-CATALYZED REDUCTION OF THE HNE-GLUTATHIONE CONJUGATES IN REGULATING CELL GROWTH J. Biol. Chem., June 30, 2006; 281(26): 17652 - 17660. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J. Pagano and M. J. Haurani Vascular Cell Locomotion: Osteopontin, NADPH Oxidase, and Matrix Metalloproteinase-9 Circ. Res., June 23, 2006; 98(12): 1453 - 1455. [Full Text] [PDF]
|
|
|
|
|
|
M. Weaver, J. Liu, D. Pimentel, D. J. Reddy, P. Harding, E. L. Peterson, and P. J. Pagano Adventitial delivery of dominant-negative p67phox attenuates neointimal hyperplasia of the rat carotid artery Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1933 - H1941. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Ardanaz and P. J. Pagano Hydrogen peroxide as a paracrine vascular mediator: regulation and signaling leading to dysfunction. Experimental Biology and Medicine, March 1, 2006; 231(3): 237 - 251. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 L. Cheng, W. Cao, C. Fiocchi, J. Behar, P. Biancani, and K. M. Harnett In vitro model of acute esophagitis in the cat Am J Physiol Gastrointest Liver Physiol, November 1, 2005; 289(5): G860 - G869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 T. Suvorava, N. Lauer, S. Kumpf, R. Jacob, W. Meyer, and G. Kojda Endogenous Vascular Hydrogen Peroxide Regulates Arteriolar Tension In Vivo Circulation, October 18, 2005; 112(16): 2487 - 2495. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. H.H. Chan, K.-S. Hsu, C.-C. Huang, L.-L. Wang, C.-C. Ou, and J. Y.H. Chan NADPH Oxidase-Derived Superoxide Anion Mediates Angiotensin II-Induced Pressor Effect via Activation of p38 Mitogen-Activated Protein Kinase in the Rostral Ventrolateral Medulla Circ. Res., October 14, 2005; 97(8): 772 - 780. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. De Ciuceis, F. Amiri, P. Brassard, D. H. Endemann, R. M. Touyz, and E. L. Schiffrin Reduced Vascular Remodeling, Endothelial Dysfunction, and Oxidative Stress in Resistance Arteries of Angiotensin II-Infused Macrophage Colony-Stimulating Factor-Deficient Mice: Evidence for a Role in Inflammation in Angiotensin-Induced Vascular Injury Arterioscler. Thromb. Vasc. Biol., October 1, 2005; 25(10): 2106 - 2113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Zuo, M. Ushio-Fukai, S. Ikeda, L. Hilenski, N. Patrushev, and R. W. Alexander Caveolin-1 Is Essential for Activation of Rac1 and NAD(P)H Oxidase After Angiotensin II Type 1 Receptor Stimulation in Vascular Smooth Muscle Cells: Role in Redox Signaling and Vascular Hypertrophy Arterioscler. Thromb. Vasc. Biol., September 1, 2005; 25(9): 1824 - 1830. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. K. Jagadeesha, T. E. Lindley, J. DeLeon, R. V. Sharma, F. Miller, and R. C. Bhalla Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats Am J Physiol Heart Circ Physiol, September 1, 2005; 289(3): H1047 - H1053. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Berg Increased counteracting effect of eNOS and nNOS on an {alpha}1-adrenergic rise in total peripheral vascular resistance in spontaneous hypertensive rats Cardiovasc Res, September 1, 2005; 67(4): 736 - 744. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Zmijewski, D. R. Moellering, C. L. Goffe, A. Landar, A. Ramachandran, and V. M. Darley-Usmar Oxidized LDL induces mitochondrially associated reactive oxygen/nitrogen species formation in endothelial cells Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H852 - H861. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. L. Huang Unraveling the Links Between Diabetes, Obesity, and Cardiovascular Disease Circ. Res., June 10, 2005; 96(11): 1129 - 1131. [Full Text] [PDF]
|
|
|
|
 |
|
 G. Desideri, M. De Simone, L. Iughetti, T. Rosato, M. L. Iezzi, M. C. Marinucci, V. Cofini, G. Croce, G. Passacquale, S. Necozione, et al. Early Activation of Vascular Endothelial Cells and Platelets in Obese Children J. Clin. Endocrinol. Metab., June 1, 2005; 90(6): 3145 - 3152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Akishita, K. Nagai, H. Xi, W. Yu, N. Sudoh, T. Watanabe, M. Ohara-Imaizumi, S. Nagamatsu, K. Kozaki, M. Horiuchi, et al. Renin-Angiotensin System Modulates Oxidative Stress-Induced Endothelial Cell Apoptosis in Rats Hypertension, June 1, 2005; 45(6): 1188 - 1193. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 T. M. Griffith, A. T. Chaytor, L. M. Bakker, and D. H. Edwards 5-Methyltetrahydrofolate and tetrahydrobiopterin can modulate electrotonically mediated endothelium-dependent vascular relaxation PNAS, May 10, 2005; 102(19): 7008 - 7013. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. I. Mendez, W. J. Nicholson, and W. R. Taylor SOD Isoforms and Signaling in Blood Vessels: Evidence for the Importance of ROS Compartmentalization Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 887 - 888. [Full Text] |