title: Tetrahydrobiopterin in cardiovascular health and disease.
abstract: Tetrahydrobiopterin (BH4) functions as a cofactor for several important enzyme systems, and considerable evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of cardiovascular health and disease. BH4 bioavailability is determined by a balance of enzymatic de novo synthesis and recycling, versus degradation in the setting of oxidative stress. Augmenting vascular BH4 levels by pharmacological supplementation has been shown in experimental studies to enhance NO bioavailability. However, it has become more apparent that the role of BH4 in other enzymatic pathways, including other NOS isoforms and the aromatic amino acid hydroxylases, may have a bearing on important aspects of vascular homeostasis, inflammation, and cardiac function. This article reviews the role of BH4 in cardiovascular development and homeostasis, as well as in pathophysiological processes such as endothelial and vascular dysfunction, atherosclerosis, inflammation, and cardiac hypertrophy. We discuss the therapeutic potential of BH4 in cardiovascular disease states and attempt to address how this modulator of intracellular NO-redox balance may ultimately provide a powerful new treatment for many cardiovascular diseases.
authors.affiliation: Division of Cardiovascular Medicine, British Heart Foundation Centre of Research Excellence, University of Oxford , John Radcliffe Hospital, Oxford, United Kingdom .
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Bendall
authors.forename: Gillian
authors.initials: G
authors.lastname: Douglas
authors.forename: Eileen
authors.initials: E
authors.lastname: McNeill
authors.forename: Keith M
authors.initials: KM
authors.lastname: Channon
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Crabtree
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism; D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism; D006332:Cardiomegaly / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000378:metabolism*; D002319:Cardiovascular System / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010084:Oxidation-Reduction
chemical_list: D001708:Biopterins; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin