期刊
VASCULAR PHARMACOLOGY
卷 58, 期 3, 页码 219-230出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.vph.2012.08.002
关键词
Tetrahydrobiopterin; GTP cyclohydrolase 1; Nitric oxide synthase; Endothelial
资金
- Biotechnology and Biological Sciences Research Council [BB/E527098/1] Funding Source: Medline
- British Heart Foundation [PG/09/073/27953] Funding Source: Medline
- BBSRC [BB/E527098/1] Funding Source: UKRI
- Biotechnology and Biological Sciences Research Council [BB/E527098/1] Funding Source: researchfish
- British Heart Foundation [PG/09/073/27953] Funding Source: researchfish
6R L-erythro-5,6,7,8-tetrahydrobiopterin (BH4) is an essential cofactor for several enzymes including phenylalanine hydroxylase and the nitric oxide synthases (NOS). Oral supplementation of BH4 has been successfully employed to treat subsets of patients with hyperphenylalaninaemia. More recently, research efforts have focussed on understanding whether BH4 supplementation may also be efficacious in cardiovascular disorders that are underpinned by reduced nitric oxide bioavailability. Whilst numerous preclinical and clinical studies have demonstrated a positive association between enhanced BH4 and vascular function, the efficacy of orally administered BH4 in human cardiovascular disease remains unclear. Furthermore, interventions that limit BH4 bioavailability may provide benefit in diseases where nitric oxide over production contributes to pathology. This review describes the pathways involved in BH4 bio-regulation and discusses other endogenous mechanisms that could be harnessed therapeutically to manipulate vascular BH4 levels. (C) 2012 Elsevier Inc. All rights reserved.
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