Tetrahydrobiopterin: regulator of endothelial nitric oxide synthase in vascular disease.
In vascular disease states such as atherosclerosis and diabetes, endothelial nitric oxide (NO) bioactivity is reduced and oxidative stress is increased, resulting in endothelial dysfunction. Recent studies suggest that changes in the activity and regulation of endothelial NO synthase by its cofactor tetrahydrobiopterin (BH4) is an important contributor to endothelial dysfunction. Pharmacologic studies and more recent insights from genetically modified mouse models have improved the understanding of the mechanistic role and importance of BH4 in vascular disease pathogenesis. Targeting BH4 may provide new therapeutic strategies in vascular disease.
Channon
Keith M
KM
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, United Kingdom. keith.channon@cardiov.ox.ac.uk
D000818:Animals; D001708:Biopterins / Q000031:analogs & derivatives* / Q000172:deficiency / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000201:enzymology* / Q000503:physiopathology; D006801:Humans; D051379:Mice; D023421:Models, Animal; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D014652:Vascular Diseases / Q000201:enzymology* / Q000503:physiopathology
D001708:Biopterins; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; C003402:sapropterin