Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19:2922-2927
© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Physiological Increments in Plasma Homocysteine Induce Vascular Endothelial Dysfunction in Normal Human Subjects
From the National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital (J.C.C., J.S.K.), and DDRC, St Bartholomew’s and the Royal London School of Medicine & Dentistry, Queen Mary and Westfield College (O.A.O.), London, UK.
Correspondence to Dr J.S. Kooner, MD, FRCP, National Heart and Lung Institute, Imperial College School of Medicine, Hammersmith Hospital, Du Cane Rd, London W12 0NN, UK. E-mail j.kooner{at}ic.ac.uk
Abstract—We hypothesized that physiological increments in plasma homocysteine after low-dose oral methionine or dietary animal protein induce vascular endothelial dysfunction and that there is a graded, inverse relationship between homocysteine concentration and endothelial function. We studied 18 healthy volunteers aged 18 to 59 years. Brachial artery flow-mediated and glyceryltrinitrate-induced dilatation were measured after 1) oral L-methionine (10, 25, and 100 mg/kg), 2) dietary animal protein (lean chicken 551±30 g, comprising 3.2±0.2 g methionine), and 3) methionine-free amino acid mix (100 mg/kg). Methionine (10, 25, and 100 mg/kg) induced a dose-related increase in homocysteine (9.4±1.3 to 12.2±2.1, 17.6±2.6, and 26.1±4.2 µmol/L, respectively; P<0.001) and a reduction in flow-mediated dilatation (4.1±0.8 to 2.1±0.8, 0.3±0.8, and -0.7±0.8%, respectively; P<0.001) at 4 hours. Compared with usual meal, animal protein increased plasma homocysteine (9.6±0.8 to 11.2±0.9 µmol/L, P=0.005) and reduced flow-mediated dilatation (4.5±0.7% to 0.9±0.6%, P=0.003). Methionine-free amino acid mix did not induce any changes. Glyceryltrinitrate-induced dilatation was unchanged throughout. In this study, small physiological increments in plasma homocysteine after low-dose methionine and dietary animal protein induced vascular endothelial dysfunction. We propose that protein intake–induced increments in plasma homocysteine may have deleterious effects on vascular function and contribute to the development and progression of atherosclerosis.
Key Words: homocysteine • endothelium • methionine • dietary protein
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