Arginine and Adhesion Molecules - Adhesion Molecules - page 106

of vessel walls in hypercholesterolemic animals is enhanced monocyte adherence
to the endothelium, which occurs within 1 wk of initiation of a high-cholesterol
diet. h is event is thought to be mediated by reduced activity of NO in
accordance with increased expression of endothelial surface adhesion molecules
and chemotactic proteins induced by hypercholesterolemia. A study by Tsao
et al. (1994) investigated whether L-Arg attenuated endothelial adhesiveness in
hypercholesterolemia. Rabbits were fed chow, a 1% high-cholesterol diet, a high-
cholesterol diet supplemented with 2.25% L-Arg HCl in drinking water, or a
normal diet with an NOS inhibitor. At er 2 wk, thoracic aortas were harvested and
placed in a culture dish with the endothelial surface exposed to medium containing
monocytoid cells. h ey found that monocytoid cell binding to aortic endothelium
was signii cantly increased in the high-cholesterol and NOS-inhibitor groups.
Binding was markedly reduced in Arg-fed hypercholesterolemic rabbits. h ese
results suggest that hypercholesterolemia enhances the adhesiveness of monocytes
to the aortic endothelium, and this ef ect is attenuated by dietary L-Arg. Inhibition
of NO synthesis enhances monocyte binding indicating that endothelium-derived
NO plays an important role in regulating the adhesiveness of monocytes to the
endothelium. In an in vitro study, Adams et al. (1997) investigated the ef ects of
Arg on monocyte adhesion to ECs and endothelial expression of cell adhesion
molecules. Human umbilical vein endothelial cells (HUVECs) and monocytes
were obtained from healthy human volunteers who had no clinical evidence of
cardiovascular disease. Conl uent EC monolayers or monocytes were treated
with various concentrations of Arg (0, 100, and 1000 μM) or 100 μM Arg with
NG-monomethyl-L-arginine (L-NMMA, a non-selective NOS inhibitor) for
24 hr before the adhesion assays. Subsequently, monocytes were incubated with
HUVECs for 1 hr at 37°C, and adhesion was measured by light microscopy. h ey
found that, compared to the control, monocyte adhesion was reduced by Arg and
increased by L-NMMA. Surface expression of intracellular adhesion molecule
(ICAM)-1 by HUVECs was reduced at both concentrations of Arg compared
to the control in both the basal and interleukin-1 beta-stimulated states, which
correlated with decreased levels of mRNA. Expression of vascular cell adhesion
molecule (VCAM)-1 was reduced in the stimulated state and only in the presence
of 1000 μM Arg. In a prospective, double-blind, randomized crossover trial, 10
men with coronary atherosclerosis took Arg (7 g three times a day) or a placebo
for 3 d each, with a washout period of 10 d. Serum from six of the ten subjects
at er Arg and placebo was then added to conl uent monolayers of HUVECs for
24 hr, and monocytes were added and cell adhesion assessed. h ey found that
adhesion was reduced following L-Arg administration compared to the placebo
(Adams et al. 1997).