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Cardiovascular Research 2000 47(3):465-474; doi:10.1016/S0008-6363(00)00086-9
© 2000 by European Society of Cardiology
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Copyright © 2000, European Society of Cardiology

Mechanisms of the pro- and anti-oxidant actions of nitric oxide in atherosclerosis

Rakesh P. Patela,b, Anna-Liisa Levonenc, Jack H. Crawfordb and Victor M. Darley-Usmara,b,*

aCenter for Free Radical Biology, Molecular and Cellular Division, University of Alabama at Birmingham, Volker Hall, Room G038, 1670 University Boulevard, Birmingham, AL 35294-0019, USA
bDepartment of Pathology, Molecular and Cellular Division, University of Alabama at Birmingham, Volker Hall, Room G038, 1670 University Boulevard, Birmingham, AL 35294-0019, USA
cHospital for Children and Adolescents, University of Helsinki, FIN-00029 Helsinki, Finland

* Corresponding author. Tel.: +1-205-975-9686; fax: +1-205-934-1775 darley{at}path.uab.edu

The association of nitric oxide (NO) with cardiovascular disease has long been recognized and the extensive research on this topic has revealed both pro- and anti-atherosclerotic effects. While these contradictory findings were initially perplexing recent studies offer molecular mechanisms for the integration of these data in the context of our current understanding of the biochemistry of NO. The essential findings are that the biochemical properties of NO allow its exploitation as both a cell signaling molecule, through its interaction with redox centers in heme proteins, and an extremely rapid reaction with other biologically relevant free radicals. The direct reaction of NO with free radicals can have either pro- or antioxidant effects. In the cell, antioxidant properties of NO can be greatly amplified by the activation of signal transduction pathways that lead to the increased synthesis of endogenous antioxidants or down regulate responses to pro-inflammatory stimuli. These findings will be discussed in the context of atherosclerosis.

KEYWORDS ROS, reactive oxygen species; RNS, reactive nitrogen species; NO, nitric oxide; O2–, superoxide anion radical; ONOO–, peroxynitrite; LDL, low-density lipoprotein; JNK, N-terminal cJun kinase; MAP kinase; mitogen activated protein kinase; VCAM, vascular cell adhesion molecule; eNOS; endothelial nitric oxide synthase; GSH, glutathione; GCS, {gamma}-glutamylcysteine synthetase; iNOS, inducible nitric oxide synthase; nNOS, neuronal nitric oxide synthase; NAC, N-acetylcysteine; PDGF, platelet derived growth factor; MCP-1, monocyte chemoattractant protein-1; ECAM, endothelial cell adhesion molecule; NF-{kappa}B, nuclear factor-{kappa}B


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