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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:397.)
© 2004 American Heart Association, Inc.

Editorials

Tetrahydrobiopterin: Mediator of Endothelial Protection

Zvonimir S. Katusic; Livius V. d’Uscio

From the Department of Anesthesiology and Molecular Pharmacology, Mayo Clinic, Rochester, MN.

Correspondence to Zvonimir S. Katusic, Department of Anesthesiology and Molecular Pharmacology, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905. Email katusic.zvonimir@mayo.edu

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

During the past twenty years, the essential role of endothelial cells in preservation of vascular homeostasis has been well established.^1,2 Protection of the vascular endothelium against harmful influences of circulating substances including excessive levels of lipids has been a major therapeutic approach in prevention of atherosclerosis. While endothelial dysfunction, defined as a loss of biologically active nitric oxide (NO) produced in the endothelium, has been recognized as a prime target for prevention and reversal of atherosclerotic process, identification of exact molecular mechanisms responsible for the loss of endothelial NO have been more difficult to determine. In the current issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Alp et al³ report a series of elegant studies on genetically modified mice supporting the concept that NO synthase cofactor, tetrahydrobiopterin (Figure 1), is an important vascular protective molecule. The beneficial effect of tetrahydrobiopterin in apolipoprotein E (ApoE)-deficient mice appears to be mediated by preservation of endothelial nitric oxide synthase (eNOS) activity and production of nitric oxide in endothelial cells.

View larger version (20K): [in this window] [in a new window]   The major steps of tetrahydrobiopterin biosynthesis. GTP=guanosine 5'-triphosphate.

See page 445

In the early 1990s it was recognized that in the presence of suboptimal concentrations of tetrahydrobiopterin, activation of purified neuronal nitric oxide synthase (nNOS) causes "uncoupling of NOS" with subsequent increase in production of superoxide anions.^4,5 These findings have been confirmed and extended to eNOS.^6–8 This concept captured the imagination of vascular biologists for several reasons: (1) impaired biosynthesis of tetrahydrobiopterin can help to explain reduced production of NO and endothelial . . . [Full Text of this Article]

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