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(Hypertension. 2008;51:28.)
© 2008 American Heart Association, Inc.
Editorial Commentaries |
From the Division of Cardiology, Department of Medicine, Emory University School of Medicine and Atlanta Veterans Administration Hospital, Atlanta, Ga.
Correspondence to David G. Harrison, Division of Cardiology, Emory University School of Medicine, 1639 Pierce Dr, Room 319 WMB, Atlanta, GA 30322. E-mail dharr02@emory.edu
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
The superoxide dismutases (SODs), which catalyze the dismutation of 2 superoxide anions to hydrogen peroxide and oxygen, represent major antioxidant mechanisms in single-cell organisms, plants, bacteria and eukaryotes. In mammalian cells, there are 3 forms of SOD that include the mitochondrial manganese SOD (MnSOD or SOD2), the cytoplasmic SOD that is a copper/zinc-containing enzyme (Cu/Zn SOD or SOD1), and an extracellular SOD that is also a copper/zinc-containing enzyme (ecSOD or SOD3). The ecSOD is unique in that it is actively secreted via the trans-Golgi network and binds to glycosaminoglycans in the vascular extracellular matrix and to the extracellular protein fibrillin 5.1 In most tissues, the amount of ecSOD is very small, on the order of 1% to 5% of the total SOD. In contrast, blood vessels, the lung, and to a lesser extent, the heart contain substantial amounts of this enzyme. The ecSOD is therefore of particular interest to investigators interested in cardiovascular and pulmonary biology. Overexpression of ecSOD protects mice against lung damage, and mice lacking ecSOD are predisposed to lung injury caused by hyperoxia. Between 30% and 50% of the total SOD in blood vessels is in this extracellular form, and mice lacking this enzyme have vascular dysfunction and are predisposed to hypertension.2
In cardiovascular tissues and, likely the lung, an important role of the SODs is to protect NO against oxidative inactivation by superoxide. Both NO and superoxide are free radicals with unpaired electrons in their outer orbitals and react with one another in a diffusion-limited
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