Mildly elevated homocysteine concentrations impair endothelium dependent vasodilation in hypercholesterolemic patients

Schlaich, Markus P. and John, Stefan and Jacobi, Johannes and Lackner, Karl J. and Schmieder, Roland E. (2000) Mildly elevated homocysteine concentrations impair endothelium dependent vasodilation in hypercholesterolemic patients. ATHEROSCLEROSIS, 153 (2). pp. 383-389. ISSN 0021-9150, 1879-1484

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Abstract

Background: Elevated low density lipoproteins (LDL)-cholesterol and homocysteine levels have both been found to be associated with an increased risk for atherosclerotic vascular disease. To assess the effects of elevated homocysteine levels in hypercholesterolemic subjects on endothelial function, we examined basal and stimulated nitric oxide (NO) mediated vasodilation in the forearm vascular bed in hypercholesterolemic subjects with normal or elevated homocysteine levels. Methods: Twenty-seven white subjects (age: 48 +/- 12 years) with elevated LDL-cholesterol (greater than or equal to 160 mg/dl) were divided into two groups with normal (12 = 11) Or mildly elevated (n = 16) homocysteine plasma concentration. We used strain gauge plethysmography to measure changes in forearm blood flow in response to intraarterial administration of increasing doses of acetylcholine (3, 12, 24, 48 mug/min), sodium nitroprusside (200, 800, 3200 ng/min), and N-monomethyl L-arginine (L-NMMA) (1, 2, 4 mu mol/min). Total homocysteine plasma concentrations were determined by high performance liquid chromatography fluorimetry. Results: Endothelium independent vascular relaxation tested by i.a. sodium nitroprusside and changes in forearm blood flow after i.a. L-NMMA indicating basal production and release of nitric oxide were similar between the two groups with normal or elevated homocysteine levels. In contrast, endothelium dependent vasodilation as assessed by the administration of i.a. acetylcholine differed between the groups with normal or elevated homocysteine levels for all doses tested (MANOVA P < 0.01: ACH 48 <mu>g/min: 480 +/- 237% with normal vs 234 +/- 130% with elevated homocysteine; P < 0.002). This was significant even after taking possible covariates such as age, blood pressure, body mass index, LDL-, high density lipoproteins (HDL)-cholesterol, and trigylcerides into account (MANOVA P < 0.02), Conclusions: From our study we conclude that homocysteine impairs endothelium dependent vasodilation in subjects with elevated LDL-cholesterol levels. The most intriguing finding is that even mildly elevated homocysteine levels seem to be of crucial importance for deterioration of endothelial function, especially if other cardiovascular risk factors such as hypercholesterolemia preexist. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

Item Type: Article
Uncontrolled Keywords: ARTERIAL OCCLUSIVE DISEASE; INDEPENDENT RISK FACTOR; EARLY ATHEROSCLEROSIS; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; LOWERING THERAPY; CORONARY; DYSFUNCTION; HUMANS; HYPERHOMOCYST(E)INEMIA; homocysteine; hypercholesterolemia; endothelium; nitric oxide; atherosclerosis; lipids; foreram blood flow
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 14 Mar 2022 06:57
Last Modified: 14 Mar 2022 06:57
URI: https://pred.uni-regensburg.de/id/eprint/41988

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