© 2000 American Heart Association, Inc.
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Oxidant Signaling in Vascular Cell Growth, Death, and Survival
A Review of the Roles of Reactive Oxygen Species in Smooth Muscle and Endothelial Cell Mitogenic and Apoptotic Signaling
From The Johns Hopkins University School of Medicine, Baltimore, Md.
Correspondence to Kaikobad Irani, MD, The Johns Hopkins University School of Medicine, Ross 1023, 720 Rutland Ave, Baltimore, MD 21205. E-mail kirani{at}mail.jhmi.edu
Abstract—Reactive oxygen species (ROS) have been traditionally regarded as toxic byproducts of aerobic metabolism. However, ROS can also act as intracellular signaling molecules in vascular cells. ROS can mediate phenotypes in vascular endothelial and smooth muscle cells that may be considered both physiological and pathophysiological. Among these are growth, apoptosis, and survival. The specific response elicited by reactive oxygen intermediaries is determined by their specific intracellular target(s). This, in turn, is dependent on the species of oxidant(s) produced, the source and therefore subcellular localization of the oxidant(s), the kinetics of production, and the quantities produced. A fuller understanding of how ROS regulate mitogenesis and apoptosis in vascular smooth muscle and endothelial cells will permit the development of novel strategies to modify or prevent vascular diseases in which these phenotypes predominate.
Key Words: reactive oxygen species • intracellular signaling
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Y. Shizukuda and P. M. Buttrick Oxygen free radicals and heart failure: new insight into an old question Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L237 - L238. [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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C. Mueller, S. Baudler, H. Welzel, M. Bohm, and G. Nickenig Identification of a Novel Redox-Sensitive Gene, Id3, Which Mediates Angiotensin II-Induced Cell Growth Circulation, May 21, 2002; 105(20): 2423 - 2428. [Abstract] [Full Text] [PDF]
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M. Potente, U. R. Michaelis, B. Fisslthaler, R. Busse, and I. Fleming Cytochrome P450 2C9-induced Endothelial Cell Proliferation Involves Induction of Mitogen-activated Protein (MAP) Kinase Phosphatase-1, Inhibition of the c-Jun N-terminal Kinase, and Up-regulation of Cyclin D1 J. Biol. Chem., May 3, 2002; 277(18): 15671 - 15676. [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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M. Katsuyama, C. Fan, and C. Yabe-Nishimura NADPH Oxidase Is Involved in Prostaglandin F2alpha -induced Hypertrophy of Vascular Smooth Muscle Cells. INDUCTION OF NOX1 BY PGF2alpha J. Biol. Chem., April 12, 2002; 277(16): 13438 - 13442. [Abstract] [Full Text] [PDF]
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C. Li and R. M. Jackson Reactive species mechanisms of cellular hypoxia-reoxygenation injury Am J Physiol Cell Physiol, February 1, 2002; 282(2): C227 - C241. [Abstract] [Full Text] [PDF]
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H. P. Souza, X. Liu, A. Samouilov, P. Kuppusamy, F. R. M. Laurindo, and J. L. Zweier Quantitation of superoxide generation and substrate utilization by vascular NAD(P)H oxidase Am J Physiol Heart Circ Physiol, February 1, 2002; 282(2): H466 - H474. [Abstract] [Full Text] [PDF]
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F. TOSETTI, N. FERRARI, S. DE FLORA, and A. ALBINI Angioprevention': angiogenesis is a common and key target for cancer chemopreventive agents FASEB J, January 1, 2002; 16(1): 2 - 14. [Abstract] [Full Text] [PDF]
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X.-m. Liu, G. B. Chapman, H. Wang, and W. Durante Adenovirus-Mediated Heme Oxygenase-1 Gene Expression Stimulates Apoptosis in Vascular Smooth Muscle Cells Circulation, January 1, 2002; 105(1): 79 - 84. [Abstract] [Full Text] [PDF]
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C. Berry, R. Touyz, A. F. Dominiczak, R. C. Webb, and D. G. Johns Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide Am J Physiol Heart Circ Physiol, December 1, 2001; 281(6): H2337 - H2365. [Abstract] [Full Text] [PDF]
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G. Zalba, G. S. Jose, M. U. Moreno, M. A. Fortuno, A. Fortuno, F. J. Beaumont, and J. Diez Oxidative Stress in Arterial Hypertension: Role of NAD(P)H Oxidase Hypertension, December 1, 2001; 38(6): 1395 - 1399. [Abstract] [Full Text] [PDF]
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L. Rossig, J. Hoffmann, B. Hugel, Z. Mallat, A. Haase, J.-M. Freyssinet, A. Tedgui, A. Aicher, A. M. Zeiher, and S. Dimmeler Vitamin C Inhibits Endothelial Cell Apoptosis in Congestive Heart Failure Circulation, October 30, 2001; 104(18): 2182 - 2187. [Abstract] [Full Text] [PDF]
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D. R. S. Steiner, N. C. Gonzalez, and J. G. Wood Leukotriene B4 promotes reactive oxidant generation and leukocyte adherence during acute hypoxia J Appl Physiol, September 1, 2001; 91(3): 1160 - 1167. [Abstract] [Full Text] [PDF]
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M. V. Gurjar, J. DeLeon, R. V. Sharma, and R. C. Bhalla Mechanism of inhibition of matrix metalloproteinase-9 induction by NO in vascular smooth muscle cells J Appl Physiol, September 1, 2001; 91(3): 1380 - 1386. [Abstract] [Full Text] [PDF]
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S. L. Lee, A. R. Simon, W. W. Wang, and B. L. Fanburg H2O2 signals 5-HT-induced ERK MAP kinase activation and mitogenesis of smooth muscle cells Am J Physiol Lung Cell Mol Physiol, September 1, 2001; 281(3): L646 - L652. [Abstract] [Full Text] [PDF]
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 T.-H. Hung, J. N. Skepper, and G. J. Burton In Vitro Ischemia-Reperfusion Injury in Term Human Placenta as a Model for Oxidative Stress in Pathological Pregnancies Am. J. Pathol., September 1, 2001; 159(3): 1031 - 1043. [Abstract] [Full Text] [PDF]
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H. D. Intengan and E. L. Schiffrin Vascular Remodeling in Hypertension: Roles of Apoptosis, Inflammation, and Fibrosis Hypertension, September 1, 2001; 38(3): 581 - 587. [Abstract] [Full Text] [PDF]
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 A. D. Schecter, A. B. Berman, L. Yi, A. Mosoian, C. M. McManus, J. W. Berman, M. E. Klotman, and M. B. Taubman HIV envelope gp120 activates human arterial smooth muscle cells PNAS, August 10, 2001; (2001) 181328798. [Abstract] [Full Text] [PDF]
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 G. Lesage, S. Glaser, Y. Ueno, D. Alvaro, L. Baiocchi, N. Kanno, J. L. Phinizy, H. Francis, and G. Alpini Regression of cholangiocyte proliferation after cessation of ANIT feeding is coupled with increased apoptosis Am J Physiol Gastrointest Liver Physiol, July 1, 2001; 281(1): G182 - G190. [Abstract] [Full Text] [PDF]
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 W. Liu, Y. Liu, and W. L. Lowe Jr. The Role of Phosphatidylinositol 3-Kinase and the Mitogen-Activated Protein Kinases in Insulin-Like Growth Factor-I-Mediated Effects in Vascular Endothelial Cells Endocrinology, May 1, 2001; 142(5): 1710 - 1719. [Abstract] [Full Text]
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Z. Chen, K. W. Woodburn, C. Shi, D. C. Adelman, C. Rogers, and D. I. Simon Photodynamic Therapy With Motexafin Lutetium Induces Redox-Sensitive Apoptosis of Vascular Cells Arterioscler Thromb Vasc Biol, May 1, 2001; 21(5): 759 - 764. [Abstract] [Full Text] [PDF]
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 M.-S. Zhou, A. Adam, and L. Raij Review: Interaction among angiotensin II, nitric oxide and oxidative stress Journal of Renin-Angiotensin-Aldosterone System, March 1, 2001; 2(1_suppl): S59 - S63. [PDF]
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F. C. Luft Workshop: Mechanisms and Cardiovascular Damage in Hypertension Hypertension, February 1, 2001; 37(2): 594 - 598. [Abstract] [Full Text] [PDF]
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A. D. Schecter, A. B. Berman, L. Yi, A. Mosoian, C. M. McManus, J. W. Berman, M. E. Klotman, and M. B. Taubman HIV envelope gp120 activates human arterial smooth muscle cells PNAS, August 28, 2001; 98(18): 10142 - 10147. [Abstract] [Full Text] [PDF]
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R. A. Forbes, C. Steenbergen, and E. Murphy Diazoxide-Induced Cardioprotection Requires Signaling Through a Redox-Sensitive Mechanism Circ. Res., April 27, 2001; 88(8): 802 - 809. [Abstract] [Full Text] [PDF]
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G. Cuda, R. Paterno, R. Ceravolo, M. Candigliota, N. Perrotti, F. Perticone, M. C. Faniello, F. Schepis, A. Ruocco, E. Mele, et al. Protection of Human Endothelial Cells From Oxidative Stress: Role of Ras-ERK1/2 Signaling Circulation, February 26, 2002; 105(8): 968 - 974. [Abstract] [Full Text] [PDF]
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