Demonstration of rapid onset vascular endothelial dysfunction after hyperhomocysteinemia : An effect reversible with vitamin C therapy

• Published in: Circulation (New York, N.Y.) N.Y.), 1999-03, Vol.99 (9), p.1156-1160
• Main Authors: CHAMBERS, J. C, MCGREGOR, A, JEAN-MARIE, J, OBEID, O. A, KOONER, J. S
• Format: Article
• Language: English
• Subjects: Adult; Ascorbic Acid - therapeutic use; Atherosclerosis (general aspects, experimental research); Biological and medical sciences; Blood and lymphatic vessels; Blood Flow Velocity - drug effects; Brachial Artery - physiopathology; Cardiology. Vascular system; Endothelium, Vascular - drug effects; Endothelium, Vascular - physiopathology; Female; Homocysteine - blood; Humans; Hyperhomocysteinemia - drug therapy; Hyperhomocysteinemia - physiopathology; Male; Medical sciences; Methionine - administration & dosage; Middle Aged; Oxidative Stress - drug effects; Time Factors
• ISSN: 0009-7322; 1524-4539
• DOI: 10.1161/01.CIR.99.9.1156

Hyperhomocysteinemia is a major and independent risk factor for vascular disease. The mechanisms by which homocysteine promotes atherosclerosis are not well understood. We hypothesized that elevated homocysteine concentrations are associated with rapid onset endothelial dysfunction, which is mediated through oxidant stress mechanisms and can be inhibited by the antioxidant vitamin C. We studied 17 healthy volunteers (10 male and 7 female) aged 33 (range 21 to 59) years. Brachial artery diameter responses to hyperemic flow (endothelium dependent), and glyceryltrinitrate (GTN, endothelium independent) were measured with high resolution ultrasound at 0 hours (fasting), 2 hours, and 4 hours after (1) oral methionine (L-methionine 100 mg/kg), (2) oral methionine preceded by vitamin C (1g/day, for 1 week), and (3) placebo, on separate days and in random order. Plasma homocysteine increased (0 hours, 12.8+/-1.4; 2 hours, 25.4+/-2.5; and 4 hours, 31. 2+/-3.1 micromol/l, P