l -Arginine Reduces Human Monocyte Adhesion to Vascular Endothelium and Endothelial Expression of Cell Adhesion Molecules

Abstract

Background Monocyte adhesion to endothelial cells is a key early event in atherogenesis. Because l -arginine has been shown to reduce atheroma and to decrease monocyte–endothelial cell adhesion in an animal model of atherosclerosis, we studied the effects of l -arginine on human monocyte adhesion to human endothelial cells and endothelial expression of cell adhesion molecules. Methods and Results Human umbilical vein endothelial cells (HUVECs) were grown to confluence, then incubated for 24 hours with arginine-deficient media to which was added saline (control), 100 or 1000 μmol/L l -arginine, 100 μmol/L d -arginine, 100 μmol/L N G -monomethyl- l -arginine (L-NMMA), or 100 μmol/L l -arginine with 100 μmol/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 assessed by an ELISA under the above conditions with and without stimulation with interleukin-1β. Expression of ICAM-1 was reduced with both concentrations of l -arginine compared with control in both the basal (43±12%, P <.01), and stimulated (46±15%, P <.01) states, which correlated with decreased levels of mRNA. Expression of VCAM-1 was reduced only in the stimulated state and only in the presence of 1000 μmol/L l -arginine (72±24%, P =.02). Conclusions l -Arginine reduces human monocyte adhesion to endothelial cells and decreases expression of certain endothelial cell adhesion molecules.