Journal
LIFE SCIENCES
Volume 81, Issue 1, Pages 1-7Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2007.04.019
Keywords
asymmetric dimethylarginine; erythrocyte deformability; atherosclerotic lesion; apolipoprotein E deficient mice
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Previous investigations have shown that the level of asymmetric dimethylarginine (ADMA) was increased in hypercholesterolemic animal and humans, and the decreased erythrocyte deformability has been suggested to be a factor contributing to atherogenesis. In the present study, we investigated the effect of ADMA, endogenous or exogenous, on atherogenesis and erythrocyte deformability in apolipoprotein E deficient (ApoE-/-) mice. On a regular chow diet, ApoE-/- mice or C57BL/6J mice at 12 weeks of age were treated with ADMA (5 mg/kg/day) for 4 weeks. Atherosclerotic lesion area, erythrocyte deformability, plasma lipids and asymmetric dimethylarginine (ADMA) level were determined. Plasma concentrations of triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C), total cholesterol (TC), ADMA, and atherosclerotic lesion area were significantly increased, and the level of plasma high-density lipoprotein-cholesterol (HDL-C), erythrocyte deformability in ApoE -/- mice were markedly decreased compared with that of C57BL/6J mice (P < 0.05 or P < 0.01). Exogenous ADMA treatment increased the plasma TG level, produced atherosclerotic lesions, and decreased erythrocyte deformability in C57BL/6J mice (P < 0.05 or P < 0.01). Treatment with exogenous ADMA further increased the plasma TG level and lesion areas, and decreased erythrocyte deformability in ApoE-/- mice. In vitro, exogenous ADMA caused a decrease of erythrocyte deformability in a concentration-dependent manner, and the effect of ADMA was reversed by L-arginine. The present results suggest that endogenous ADMA is an important contributor to the development of atherosclerosis and that reduction of erythrocyte deformability and impaired endothelial function induced by ADMA may be an important factor facilitating atherosclerotic lesions. (c) 2007 Elsevier Inc. All rights reserved.
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