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 mumol/L L-arginine, 100 mumol/L D-arginine, 100 mumol/L NG-monomethyl-L-arginine (L-NMMA), or 100 mumol/L L-arginine with 100 mumol/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-1 beta. 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 mumol/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.