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(Circulation. 2000;101:485.)
© 2000 American Heart Association, Inc.

Clinical Investigation and Reports

Effects of Methionine-Induced Hyperhomocysteinemia on Endothelium-Dependent Vasodilation and Oxidative Status in Healthy Adults

Chia-Lun Chao, MD; Tsung-Li Kuo, MD, PhD; Yuan-Teh Lee, MD, PhD

From the Department of Internal Medicine (Cardiology), National Taiwan University Hospital (C.-L.C., Y.-T.L.), and the Department of Forensic Medicine (T.-L.K.), National Taiwan University College of Medicine.

Correspondence to Yuan-Teh Lee, MD, Department of Internal Medicine (Cardiology), National Taiwan University Hospital, 7, Chung-Shan South Road, Taipei, 100, Taiwan, ROC. E-mail ytlee{at}ha.mc.ntu.edu.tw

Background—Homocysteine-mediated endothelial dysfunction has been proposed to occur via oxidative stress mechanisms in humans. However, there is controversy regarding the effects of homocysteine on endothelial function and oxidative status, which may in part result from age discrepancy across the studies. The present study was designed to investigate the aging effect on the relationship between endothelium-dependent vasodilation and oxidative status in methionine-induced hyperhomocysteinemia.

Methods and Results—Plasma homocysteine, phosphatidylcholine hydroperoxide (PCOOH), P-selectin levels, and brachial artery flow-mediated vasodilation were measured at baseline and 4 hours after an oral methionine load (0.1 g/kg) in 15 younger (21 to 40 years) and 15 older (55 to 70 years) healthy adults. Homocysteine increased from 7.3±1.3 µmol/L at baseline to 22.7±5.2 µmol/L at 4 hours in younger (P<0.001) and from 7.4±1.4 to 24.3±4.5 µmol/L in older adults (P<0.001). PCOOH levels were not significantly different between baseline and 4 hours in both groups (P=0.10 in young; P=0.14 in old). P-selectin, which is expected to increase during oxidative stress, was not changed in older (P=0.08) but decreased in younger adults (P=0.037) at 4 hours. Flow-mediated vasodilation was preserved from 13.1±2.1% at baseline to 13.5±2.8% at 4 hours in younger (P=0.49) and decreased from 12.8±2.4% to 8.5±2.8% in older adults (P<0.001).

Conclusions—The present study demonstrates that endothelial dysfunction caused by methionine-induced hyperhomocysteinemia is age-related and is mediated through impaired nitric oxide activity without change of oxidative status. Our data do not support previous hypotheses that endothelial damage by homocysteine is via oxidative stress mechanism in humans.

Key Words: endothelium • homocysteine • nitric oxide • vasodilation

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