L-ARGININE REDUCES HUMAN MONOCYTE ADHESION TO VASCULAR ENDOTHELIUM AND ENDOTHELIAL EXPRESSION OF CELL-ADHESION MOLECULES

Background Monocyte adhesion to endothelial cells is a key early event in atherogenesis. Because L-arginine has been shown to reduce atherom a and to decrease monocyte-endothelial cell adhesion in an animal mode l of atherosclerosis, we studied the effects of L-arginine on human mo nocyte adhesion to human endothelial cells and endothelial expression of cell adhesion molecules. Methods and Results Human umbilical vein e ndothelial cells (HUVECs) were grown to confluence, then incubated for 24 hours with arginine-deficient media to which was added saline (con trol), 100 or 1000 mu mol/L L-arginine, 100 mu mol/L D-arginine, 100 m u mol/L N-G-monomethyl-L-arginine (L-NMMA), or 100 mu mol/L L-arginine with 100 mu mol/L L-NMMA Human monocytes obtained by elutriation were incubated for 1 hour with HUVECs, and adhesion was measured by light microscopy. Compared with control, monocyte adhesion was reduced by L- arginine (59 +/- 10%, P=.01) and increased by L-NMMA (123+/-20%, P=.01 ). Surface expression of cell adhesion molecules by HUVECs was assesse d by an ELISA under the above conditions with and without stimulation with interleukin-1 beta. Expression of ICAM-1 was reduced with both co ncentrations of L-arginine compared with control in both the basal (43 +/- 12%, P<.01), and stimulated (46+/-15%, P=.01) states, which corre lated with decreased levels of mRNA. Expression of VCAM-1 was reduced only in the stimulated state and only in the presence of 1000 mu mol/L L-arginine (72+/-24%, P=.02). Conclusions L-Arginine reduces human mo nocyte adhesion to endothelial cells and decreases expression of certa in endothelial cell adhesion molecules.