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Semin Vasc Med 2005; 5(2): 172-182
DOI: 10.1055/s-2005-872402
Copyright © 2005 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001 USA.

Homocysteine and Endothelial Function in Human Studies

Stuart J. Moat1 , Ian F. W. McDowell1
  • 1Department of Medical Biochemistry and Immunology, Wales College of Medicine, Cardiff University and the University Hospital of Wales, Cardiff, United Kingdom
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Publication History

Publication Date:
27 July 2005 (online)

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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.

KEYWORDS

Endothelium - flow-mediated dilation - nitric oxide - tetrahydrobiopterin

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Stuart J MoatPh.D. 

Department of Medical Biochemistry and Immunology, Wales College of Medicine, Cardiff University and the University Hospital of Wales

Heath Park, Cardiff, UK, CF14 4XW