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Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2439-2444
Published online before print August 31, 2006, doi: 10.1161/01.ATV.0000243924.00970.cb
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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2439.)
© 2006 American Heart Association, Inc.


Brief Reviews

Tetrahydrobiopterin and Cardiovascular Disease

An L. Moens; David A. Kass

From the Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, Md.

Correspondence to David A. Kass, MD, Ross 835, Division of Cardiology, Johns Hopkins Medical Institutions, 720 Rutland Avenue, Baltimore, MD 21205. E-mail dkass{at}jhmi.edu

Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, which are essential in the formation of neurotransmitters, and for nitric oxide synthase. It is presently used clinically to treat some forms of phenylketonuria (PKU) that can be ameliorated by BH4 supplementation. Recent evidence supports potential cardiovascular benefits from BH4 replacement for the treatment of hypertension, ischemia-reperfusion injury, and cardiac hypertrophy with chamber remodeling. Such disorders exhibit BH4 depletion because of its oxidation and/or reduced synthesis, which can result in functional uncoupling of nitric oxide synthase (NOS). Uncoupled NOS generates more oxygen free radicals and less nitric oxide, shifting the nitroso-redox balance and having adverse consequences on the cardiovascular system. While previously difficult to use as a treatment because of chemical instability and cost, newer methods to synthesize stable BH4 suggest its novel potential as a therapeutic agent. This review discusses the biochemistry, physiology, and evolving therapeutic potential of BH4 for cardiovascular disease.

Tetrahydrobiopterin (BH4) is an essential cofactor for the aromatic amino acid hydroxylases, which are essential in the formation of neurotransmitters, and for nitric oxide synthase (NOS). BH4 replacement may help treat hypertension, ischemia-reperfusion injury, and cardiac hypertrophy with chamber remodeling, by restoring functional NOS. This review discusses BH4 biochemistry, physiology, and evolving uses to treat cardiovascular disease.


Key Words: tetrahydrobiopterin • nitric oxide synthase • atherosclerosis • inflammation




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