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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2007;27:442.)
© 2007 American Heart Association, Inc.

Editorials

Extracellular SOD Inactivation in High-Volume Hypertension

Role of Hydrogen Peroxide

Tohru Fukai

From the Departments of Medicine (Section of Cardiology) and Pharmacology, University of Illinois at Chicago.

Correspondence to Tohru Fukai, MD, PhD, Departments of Medicine (Section of Cardiology) and Pharmacology, University of Illinois at Chicago, 835 S. Wolcott, M/C868, E403MSB, Chicago, IL 60612. E-mail tfukai@uic.edu

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Excessive reactive oxygen species (ROS), especially superoxide anion (O₂^•–), contribute to the pathogenesis of many cardiovascular diseases, including hypertension. The major antioxidant defense system against O₂^•– is superoxide dismutases (SODs). In mammals, 3 isoforms of superoxide dismutase exist: the cytoplasmic CuZnSOD (SOD1), the mitochondrial MnSOD (SOD2), and the extracellular Cu/ZnSOD (SOD3, ecSOD). The ecSOD is the major SOD in the vascular extracellular space, and synthesized by vascular smooth muscle cells and fibroblasts. It is secreted and anchored to the extracellular matrix and endothelial cell surface through binding to the heparan sulfate proteoglycan, collagen, and fibulin-5.^1–3 Of note, the R213G polymorphism in the ecSOD gene, which reduces binding to endothelial surface and increases serum ecSOD levels, has been linked to an increase in cardiovascular risk.⁴

See page 470

Nitric oxide (NO^•) produced by endothelium stimulates vasodilation of vascular smooth muscle and thus exerts antihypertensive action. Because O₂^•– reacts with NO^• at almost diffusion-limited rates, ecSOD which scavenges O₂^•– in the vascular extracellular space plays an important role in regulating bioactivity of NO^•.¹ Indeed, gene transfer of ecSOD reduces O₂^•– and restores impairment of endothelium dependent relaxation, resulting in the decrease in arterial pressure in a genetic model of hypertension.⁵ Furthermore, ecSOD has peroxidase activity in which H₂O₂, the dismutation product of O₂^•–, can inactivate ecSOD by reacting with the copper center of ecSOD, thereby forming the Cu–OH radical and leading to enzyme inactivation.⁶ This effect can be prevented by scavenging the Cu–OH radical with small . . . [Full Text of this Article]

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Arterioscler Thromb Vasc Biol 2007 27: 470-477. [Abstract] [Full Text] [PDF]