The DOI matches its Crossref record; 344 of the 344 references it cites were found in a registry or an index.
Tetrahydrobiopterin in Cardiovascular Health and Disease
Open accessAbstract
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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“In addition, BH4 plays a critical role in the catalytic cycle of NOS (87, 204, 377, 904, 933, 1000, 1007).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [87]
Citations
Cites
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725
Dellinger, R. P., Levy, M. M., Carlet, J. M., Bion, J., Parker, M. M., Jaeschke, R., Reinhart, K., Angus, D. C., Brun‐Buisson, C., Beale, R. J., et al. (2007) · Intensive Care Medicine · doi:10.1007/s00134-007-0934-2 · Cited by 6,789
Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men
Ridker, P. M., Cushman, M., Stampfer, M. J., Tracy, R. P., & Hennekens, C. H. (1997) · New England Journal of Medicine · doi:10.1056/nejm199704033361401 · Cited by 5,504
Griffith, O. W. (1980) · Analytical Biochemistry · doi:10.1016/0003-2697(80)90139-6 · Cited by 4,628
Nitric oxide synthases: regulation and function
Forstermann, U., & Sessa, W. C. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehr304 · Cited by 4,409
Endothelial dysfunction in cardiovascular diseases: the role of oxidant stress
Cai, H., & Harrison, D. G. (2000) · Circulation Research · doi:10.1161/01.res.87.10.840 · Cited by 3,839
Isolation of nitric oxide synthetase, a calmodulin-requiring enzyme.
Bredt, D. S., & Snyder, S. H. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.2.682 · Cited by 3,308
Advanced Glycosylation End Products in Tissue and the Biochemical Basis of Diabetic Complications
Flier, J. S., Underhill, L. H., Brownlee, M., Cerami, A., & Vlassara, H. (1988) · New England Journal of Medicine · doi:10.1056/nejm198805193182007 · Cited by 2,512
Glutamate, nitric oxide and cell-cell signalling in the nervous system
Garthwaite, J. (1991) · Trends in Neurosciences · doi:10.1016/0166-2236(91)90022-m · Cited by 2,401
Research works printed but not linked: 6
- 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.
- Crabtree MJ, and Channon KM. Dihydrofolate reductase is required to maintain endothelial nitric oxide synthase coupling in vivo: Insights from methotrexate-treated BH4 deficient and GTPCH overexpressing mice. Nitric Oxide, 22: S30, 2010.
- Hopkins FG. Note on Yellow Pigments in Butterflies. Nature, 40: 335, 1889.
- 10.1042/bj3490353 · DOI
- 10.1172/JCI0215215 · DOI · Paper page
- 10.1172/JCI0214442 · DOI · Paper page
Cited by
Sorted by citations
Coronary Microvascular Dysfunction
Crea, F., Lanza, G. A., & Camici, P. G. (2013) · Springer eBooks · doi:10.1007/978-88-470-5367-0 · Cited by 1,295
B Vitamins and the Brain: Mechanisms, Dose and Efficacy—A Review
Kennedy, D. (2016) · Nutrients · doi:10.3390/nu8020068 · Cited by 1,055
Endothelial Cell Metabolism in Normal and Diseased Vasculature
Eelen, G., de Zeeuw, P., Simons, M., & Carmeliet, P. (2015) · Circulation Research · doi:10.1161/circresaha.116.302855 · Cited by 637
Eelen, G., de Zeeuw, P., Treps, L., Harjes, U., Wong, B. W., & Carmeliet, P. (2017) · Physiological Reviews · doi:10.1152/physrev.00001.2017 · Cited by 614
Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation
Tejero, J., Shiva, S., & Gladwin, M. T. (2019) · Physiological Reviews · doi:10.1152/physrev.00036.2017 · Cited by 541
Metadata
- Authors
- Bendall, J. K., Douglas, G., McNeill, E., Channon, K. M., & Crabtree, M. J.
- Affiliations
- John Radcliffe Hospital (GB)
- Venue
- Antioxidants & Redox Signaling
- Publisher
- SAGE Publications
- Published
- 2014-06
- Volume
- 20
- Issue
- 18
- Pages
- 3040-3077
- ISSN
- 1523-0864 (ISSN-L)
- 1557-7716
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
