This Article Full Text Full Text (PDF) All Versions of this Article: 25/4/778    most recent 01.ATV.0000157981.57694.d2v1 Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spijkerman, A.M.W. Articles by Stehouwer, C.D.A. Search for Related Content PubMed PubMed Citation Articles by Spijkerman, A.M.W. Articles by Stehouwer, C.D.A.

(Arteriosclerosis, Thrombosis, and Vascular Biology. 2005;25:778.)
© 2005 American Heart Association, Inc.

Vascular Biology

S-Adenosylmethionine and 5-Methyltetrahydrofolate Are Associated With Endothelial Function After Controlling for Confounding by Homocysteine

The Hoorn Study

A.M.W. Spijkerman; Y.M. Smulders; P.J. Kostense; R.M.A. Henry; A. Becker; T. Teerlink; C. Jakobs; J.M. Dekker; G. Nijpels; R.J. Heine; L.M. Bouter; C.D.A. Stehouwer

From the Institute for Research in Extramural Medicine (A.M.W.S., P.J.K., J.M.D., G.N., L.M.B., C.D.A.S.), Institute for Cardiovascular Research (A.M.W.S., Y.M.S., A.B., T.T., C.J.), Department of Internal Medicine (Y.M.S.), Department of Clinical Epidemiology and Biostatistics (P.J.K.), Department of Clinical Chemistry (T.T., C.J.), and Department of Endocrinology (R.J.H.), VU University Medical Center, Amsterdam; Department of Internal Medicine (R.M.A.H.), Hospital Kennemer Gasthuis, Haarlem; and Department of Internal Medicine (C.D.A.S.), Academic Hospital Maastricht, the Netherlands.

Correspondence to Y.M. Smulders, MD, PhD, Department of Internal Medicine, VU University Medical Center, PO Box 7057, 1007 MB, Amsterdam, the Netherlands. E-mail y.smulders{at}vumc.nl

Objective— To explore to what extent homocysteine, S-adenosylmethionine (SAM), S-adenosylhomocysteine, total folate, 5-methyltetrahydrofolate (5-MTHF), vitamin B12, and vitamin B6 are associated with endothelium-dependent, flow-mediated vasodilation (FMD), and whether these associations are stronger in individuals with diabetes or other cardiovascular risk factors.

Methods and Results— In this population-based study of 608 elderly people, FMD and endothelium-independent nitroglycerin-mediated dilation (NMD) were ultrasonically estimated from the brachial artery (absolute change in diameter [µm]). High SAM and low 5-MTHF were significantly associated with high and low FMD, respectively (linear regression coefficient, [95% confidence interval]): 48.57 µm (21.16; 75.98) and –32.15 µm (–59.09; –5.20), but high homocysteine was not (–15.11 µm (–42.99; 12.78). High SAM and low 5-MTHF were also significantly associated with high and low NMD, respectively. NMD explained the association of 5-MTHF with FMD but not of SAM. No interactions were observed for diabetes or cardiovascular risk factors.

Conclusions— In this elderly population, both SAM and 5-MTHF are associated with endothelial and smooth muscle cell function. The effect of homocysteine on endothelial function is relatively small compared with SAM and 5-MTHF. The relative impact of SAM, 5-MTHF, and homocysteine, and the mechanisms through which these moieties may affect endothelial and smooth muscle cell function need clarification.

We explored the associations between homocysteine, S-adenosylmethionine (SAM), and S-adenosylhomocysteine (SAH), total folate, 5-methyltetrahydrofolate (active folate, 5-MTHF), vitamin B12, vitamin B6, and endothelium-dependent flow-mediated vasodilation.

Key Words: homocysteine • S-adenosylmethionine • metabolism • folate • endothelial function

This article has been cited by other articles:

				S. P Stabler, R. H Allen, E. T Dolce, and M. A. Johnson Elevated serum S-adenosylhomocysteine in cobalamin-deficient elderly and response to treatment Am. J. Clinical Nutrition, December 1, 2006; 84(6): 1422 - 1429. [Abstract] [Full Text] [PDF]

				C. Antoniades, C. Shirodaria, N. Warrick, S. Cai, J. de Bono, J. Lee, P. Leeson, S. Neubauer, C. Ratnatunga, R. Pillai, et al. 5-Methyltetrahydrofolate Rapidly Improves Endothelial Function and Decreases Superoxide Production in Human Vessels: Effects on Vascular Tetrahydrobiopterin Availability and Endothelial Nitric Oxide Synthase Coupling Circulation, September 12, 2006; 114(11): 1193 - 1201. [Abstract] [Full Text] [PDF]