Tetrahydrobiopterin: pleiotropic roles in cardiovascular pathophysiology.
Tetrahydrobiopterin (BH4) functions as a cofactor in several important enzyme systems. Substantial evidence implicates BH4 as a key regulator of endothelial nitric oxide synthase (eNOS) in the setting of endothelial dysfunction and atherosclerosis. Investigators have now taken early steps in addressing the potential of BH4 as a therapeutic strategy. 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 cardiovascular homeostasis. Together with eNOS, these enzymes may play key roles in diverse cardiovascular disease states such as ischaemia-reperfusion injury, cardiac hypertrophy, cardiac autonomic function and pulmonary hypertension. This review provides an overview of the role of BH4 in cardiovascular pathophysiology.
Cunnington
Colin
C
Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Channon
Keith M
KM
D000818:Animals; D001341:Autonomic Nervous System / Q000201:enzymology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000502:physiology; D002312:Cardiomyopathy, Hypertrophic / Q000201:enzymology; D002318:Cardiovascular Diseases / Q000201:enzymology*; D004730:Endothelium, Vascular / Q000201:enzymology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000201:enzymology; D051379:Mice; D052250:Nitric Oxide Synthase Type III; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D015427:Reperfusion Injury / Q000201:enzymology
D001708:Biopterins; D052250:Nitric Oxide Synthase Type III; C003402:sapropterin