ENHANCED MONOCYTE TISSUE FACTOR RESPONSE AFTER EXPERIMENTAL BALLOON ANGIOPLASTY IN HYPERCHOLESTEROLEMIC RABBIT - INHIBITION WITH DIETARY L-ARGININE

Background-There is evidence that tissue factor (TF) is a major contri butor to the thrombogenicity of a ruptured atherosclerotic plaque. Nit ric oxide (NO) has antiatherogenic and antithrombotic properties. We i nvestigated whether L-arginine (L-arg), the endogenous precursor of NO , might affect the ability of monocytes to produce TF. Methods and Res ults-We studied TF expression in 18 rabbits with atherosclerosis induc ed by bilateral iliac damage and 10 weeks of a 2% cholesterol diet. Si x weeks after the initiation of the diet, an angioplasty was performed . After angioplasty, the surviving rabbits (n=15) were randomized to r eceive L-arg (2.25%) supplementation in drinking water (L-arg group, n =8) or no treatment (untreated group, n=7). TF expression was evaluate d in mononuclear cells from arterial blood in the presence and absence of endotoxin stimulation. Monocyte TF expression, as assessed with an amidolytic assay, did not differ significantly before or after the in duction of atherosclerotic lesions (87+/-15 versus 70+/-12 mU of TF/10 00 monocytes, P=NS). Endotoxin-stimulated TF activity increased signif icantly 4 weeks after angioplasty (138+/-22 versus 70+/-12 mU of TF/10 00 monocytes, P=0.02). This increase was blunted by L-arg (43+/-16 mU of TF/1000 monocytes, P=0.01). Conclusions-This study demonstrates tha t angioplasty-induced plaque rupture is associated with a marked incre ase in monocyte TF response that is blunted by the oral administration of L-arg. This suggests that the documented antithrombotic properties of NO may be related in part to an inhibitory effect on monocyte TF r esponse.