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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:1580.)
© 2008 American Heart Association, Inc.

Editorials

Targeted Increases in Endothelial Cell Superoxide Anion Production Stimulate eNOS-Dependent Nitric Oxide Production, Not Uncoupled eNOS Activity

Hao Xu; Kirkwood A. Pritchard, Jr

From the Medical College of Wisconsin, Department of Surgery, Division of Pediatric Surgery, Children’s Research Institute, Milwaukee.

Correspondence to Kirkwood A. Pritchard Jr, Medical College of Wisconsin, Department of Surgery, Division of Pediatric Surgery, Children’s Research Institute – C4420, 8701 Watertown Plank Road, Milwaukee, WI 53226. E-mail kpritch@mcw.edu

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

Every once in a while a paper comes along that makes us question our understanding of cell biology. Current theory holds that oxidative stress increases oxidation of tetrahydrobiopterin (BH4), which in turn uncouples endothelial nitric oxide synthase (eNOS) activity. Numerous publications, using a variety of experimental approaches, provide strong support for the BH4 oxidation hypothesis. Indeed, nearly 10 years ago it was shown, using purified recombinant eNOS, that loss of this critical cofactor promoted eNOS generation of superoxide anion (O₂^·–) rather than nitric oxide (^·NO) on activation.¹

See accompanying article on page 1627

The report by Zhang et al,² however, demonstrates that when vascular endothelial cells in vivo are transduced with NOX5 they responded by increasing ^·NO production rather than eNOS becoming uncoupled as might be predicted. However, these findings are consistent with an earlier study showing that hypercholesterolemia increases vascular production of nitrogen oxides but not vasodilation.³ At the time, the loss in vascular ^·NO activity in hypercholesterolemic rabbits was considered the result of marked increases in production of O₂^·–, which inactivates ^·NO rather than impairing ^·NO production.³ Although hypercholesterolemia adversely impacts the vessel wall in numerous ways, transducing NOX5 provides essentially a singular means of increasing vascular endothelial O₂^·– generation. The advantage of this approach should be clear, that the increase in O₂^·– represents a critical signaling event in the vessel wall that is separate from the confounding variable effects of oxidized lipids, inflammatory cells, or impaired high density lipoprotein function that are noted in . . . [Full Text of this Article]

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Arterioscler Thromb Vasc Biol 2008 28: 1627-1633. [Abstract] [Full Text] [PDF]