title: Homocysteine and endothelial function in human studies.
abstract: The endothelium plays a key role in the pathophysiology of vascular disease. Impaired flow-mediated dilatation (FMD) is a measure of endothelial dysfunction resulting from reduced bioavailability of nitric oxide (NO). Patients with homocystinuria manifest with impaired FMD, but in mild hyperhomocysteinemia, the evidence is conflicting. Oral loading with methionine or homocysteine impairs FMD, but it remains unproven that this effect is mediated directly by homocysteine. In addition, there is no clear consensus as to a mechanisms by which homocysteine would induce endothelial dysfunction. Folate administration lowers plasma homocysteine and enhances FMD. However, the effect of folate only appears to occur at high doses and with a time course that would indicate that it is acting by a mechanism independent of homocysteine lowering. It is possible that folate, in pharmacological doses, may enhance the NO activity by influencing NO-tetrahydrobiopterin interactions. These studies provide some insights and raise intriguing questions concerning the relationship between homocysteine, folate, and endothelial function. However, changes in FMD may not translate into vascular endpoints, and the outcomes of clinical intervention trials with different doses of folic acid are awaited with interest.
authors.affiliation: Department of Medical Biochemistry and Immunology, Wales College of Medicine, Cardiff University and the University Hospital of Wales, Cardiff, United Kingdom.
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Moat
authors.forename: Ian F W
authors.initials: IF
authors.lastname: McDowell
mesh_terms: D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D005492:Folic Acid / Q000627:therapeutic use; D006397:Hematinics / Q000627:therapeutic use; D006710:Homocysteine / Q000378:metabolism*; D006712:Homocystinuria / Q000097:blood / Q000150:complications / Q000503:physiopathology; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000150:complications / Q000503:physiopathology; D014652:Vascular Diseases / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D006397:Hematinics; D006710:Homocysteine; D005492:Folic Acid