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Tetrahydrobiopterin in Cardiovascular Health and Disease

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Bendall, Jennifer K., Douglas, Gillian, McNeill, Eileen, Channon, Keith M., Crabtree, Mark J.·2014·Antioxidants & Redox Signaling

DOI 10.1089/ars.2013.5566PMC PMC4038990

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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. Antioxid. Redox Signal. 20, 3040–3077.

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Ali ZA, , Alp N, , Tatham AL, , Greaves DR, , and Channon KM. Increased endothelial tetrahydrobiopterin synthesis reduces vein graft atherosclerosis in ApoE-knockout mice. Circulation, 112(17)II, 440, 2005.
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10.1172/JCI0215215 · DOI · Paper page
10.1172/JCI0214442 · DOI · Paper page

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Authors: Bendall, J. K., Douglas, G., McNeill, E., Channon, K. M., & Crabtree, M. J.
Affiliations: John Radcliffe Hospital (GB)
ORCID: Douglas, Gillian
McNeill, Eileen
Channon, Keith M.
Crabtree, Mark J.
Venue: Antioxidants & Redox Signaling
Publisher: SAGE Publications
Published: 2014-06
Volume: 20
Issue: 18
Pages: 3040-3077
ISSN: 1523-0864 (ISSN-L)
1557-7716
DOI: 10.1089/ars.2013.5566
PMC: PMC4038990
OpenAlex: W2092784951
Cited by: 231
References: 340
Citations by year: 2026: 12 · 2025: 21 · 2024: 15 · 2023: 22 · 2022: 26 · 2021: 20 · 2020: 21 · 2019: 18 · 2018: 18 · 2017: 21 · 2016: 15 · 2015: 12 · 2014: 9
FWCI: 1.36
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Antioxidants and Redox Signaling (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust (090532)
National Institute for Health and Care Research (NF-SI-0508-10247)
British Heart Foundation (RE/08/004, RG/12/5/29756, RG/12/5/29576)
Topics: Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
Health Sciences › Nursing › Nutrition and Dietetics › Folate and B Vitamins Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
Keywords: tetrahydrobiopterin, BH4, endothelial nitric oxide synthase, nitric oxide bioavailability, oxidative stress, aromatic amino acid hydroxylases, atherosclerosis, endothelial dysfunction, vascular dysfunction, inflammation, cardiac hypertrophy, cardiovascular disease, BH4 supplementation, cardiovascular homeostasis
MeSH terms: Biopterins, Cardiovascular Diseases, Cardiovascular System, Cardiomegaly, Humans, Inflammation, Oxidation-Reduction, Atherosclerosis, Nitric Oxide Synthase Type III

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Tetrahydrobiopterin in Cardiovascular Health and Disease

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