The regulation of vascular tetrahydrobiopterin bioavailability

TY - JOUR

T1 - The regulation of vascular tetrahydrobiopterin bioavailability

AU - Starr, Anna

AU - Hussein, Dania

AU - Nandi, Manasi

PY - 2013/3

Y1 - 2013/3

N2 - 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.

AB - 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.

KW - Nitric oxide

KW - Tetrahydrobiopterin

KW - Endotheial dysfunction

U2 - 10.1016/j.vph.2012.08.002

DO - 10.1016/j.vph.2012.08.002

M3 - Article

SN - 1537-1891

VL - 58

SP - 219

EP - 230

JO - VASCULAR PHARMACOLOGY

JF - VASCULAR PHARMACOLOGY

IS - 3

ER -