Effect of hyperhomocysteinemia induced by methionine administration on flow-mediated dilatation of the brachial artery in healthy subjects

Al-Shaer, Moutasim H.; Raghuveer, Geetha; Browning, Roger L.; Sinkey, Christine A.; Chenard, Catherine A.; Stumbo, Phyllis J.; Haynes, William G.

doi:10.1016/j.amjcard.2004.09.052

Cited by 10 publications

(7 citation statements)

References 16 publications

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“…Circulating asymmetrical dimethylarginine is independently associated with increased arterial wave reflections in subjects undergoing diagnostic coronary angiography [65]. Importantly, methionine loading acutely impairs brachial artery distensibility and this is strongly correlated with decreased endotheliumdependent flow-mediated dilatation of the brachial artery [66]. This result suggests that endothelial dysfunction increases arterial stiffness in hyperhomocysteinemia.…”

Section: Clinical Implications Of Arterial Stiffness Caused By Endothmentioning

confidence: 95%

Arterial compliance and endothelial function

Correia

Haynes²

2007

Curr Diab Rep

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Decreased arterial compliance (increased stiffness) correlates with cardiovascular events, possibly due to increased cardiac afterload caused by more rapidly reflected pulse waves. Endothelium-derived mediators regulate vascular tone and structure, both of which can markedly influence arterial stiffness. Thus, increased arterial stiffness may be a mechanism by which endothelial dysfunction predisposes to complications of atherosclerosis. Conversely, therapeutic manipulation of endothelial mediators could reduce arterial stiffness and cardiovascular events. Techniques have been developed that use measures of arterial stiffness as an index of endothelial dilator function; these may provide unique prognostic information to identify high-risk subjects.

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Section: Clinical Implications Of Arterial Stiffness Caused By Endothmentioning

confidence: 95%

Arterial compliance and endothelial function

Correia

Haynes²

2007

Curr Diab Rep

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“…The risk of death from ischemic heart disease is strongly increased for each 5-mmol/L increment in the homocysteine (Hcy) level (5,6). High Hcy levels act on endothelium-dependent vasodilatation (7,8) and elicit a negative inotropic effect on ventricular myocardium (9), and thus could represent a risk factor for CHF. HHcy has been described in hospitalized elderly subjects, associated in 30% of cases with CHF (10).…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of homocysteinemia in patients with congestive heart failure

Gibelin

Serre²,

Candito³

et al. 2006

Clinical Chemistry and Laboratory Medicine (CCLM)

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“…Patients with hyperhomocysteinemia have impaired vascular function relative to healthy controls [ 29 – 32 ]. In addition, methionine-induced hyperhomocysteinemia in healthy participants also has been shown to lead to impairment in vascular function [ 33 – 43 ].…”

Section: Introductionmentioning

confidence: 99%

Acute Effect of Folic Acid, Betaine, and Serine Supplements on Flow-Mediated Dilation after Methionine Loading: A Randomized Trial

et al. 2006

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Objectives:We investigated whether reducing post-methionine homocysteine concentrations via various treatments other than folic acid affects vascular function, as measured through flow-mediated dilation (FMD) of the brachial artery. High fasting and post-methionine homocysteine concentrations are associated with cardiovascular disease risk, but homocysteine might be a surrogate marker for low folate status.Design:This was a randomized, placebo-controlled, double-blind, crossover study.Setting:The study took place at Wageningen University in Wageningen in the Netherlands.Participants:Participants were 39 apparently healthy men and women, aged 50–70 y.Interventions:Participants ingested 10 mg of folic acid, 3 g of betaine, 5 g of serine, and placebo together with an oral methionine load. Each supplement was tested on two different days.Outcome Measures:On each of the eight treatment days, plasma homocysteine concentrations and FMD were measured before (t = 0 h, fasting) and 6 h (t = 6 h) after methionine loading.Results:The mean (± SD) fasting homocysteine concentrations averaged over the eight test days were 9.6 ± 2.1 μmol/l. Mean fasting FMD was 3.1 ± 2.4 FMD%. A methionine load with placebo increased homocysteine concentrations by 17.2 ± 9.3 μmol/l at 6 h after loading, similar to the increase following methionine loading with folic acid. A methionine load together with betaine and with serine increased homocysteine by 10.4 ± 2.8 μmol/l (p < 0.001 relative to placebo) and by 12.1 ± 8.2 μmol/l (p < 0.001 relative to placebo), respectively. Methionine loading with placebo did not affect FMD, and neither did methionine loading with folic acid, betaine, or serine; differences relative to placebo were +0.7 FMD% (95%CI, −0.6; 1.9), +0.2 FMD% (−1.0; 1.3), and +0.3 FMD% (−0.8; 1.4), respectively.Conclusions:Experimentally induced acute changes in homocysteine concentrations did not affect FMD in healthy volunteers. This implies that potential adverse effects of high homocysteine concentrations on the cardiovascular system are not mediated through vascular function. However, homocysteine or folate may affect cardiovascular disease risk through other mechanisms.

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Effect of hyperhomocysteinemia induced by methionine administration on flow-mediated dilatation of the brachial artery in healthy subjects

Cited by 10 publications

References 16 publications

Arterial compliance and endothelial function

Arterial compliance and endothelial function

Prognostic value of homocysteinemia in patients with congestive heart failure

Acute Effect of Folic Acid, Betaine, and Serine Supplements on Flow-Mediated Dilation after Methionine Loading: A Randomized Trial

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