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(Circulation. 1998;98:1776-1782.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Enhanced Monocyte Tissue Factor Response After Experimental Balloon Angioplasty in Hypercholesterolemic Rabbit: Inhibition With Dietary L-Arginine

Delphine Corseaux, PhD; Thierry Le Tourneau, MD; Isabelle Six; Michael D. Ezekowitz, MD, PhD; Eugene P. Mc Fadden, MRCPI; Thibaud Meurice, MD; Philippe Asseman, MD; Christophe Bauters, MD; ; Brigitte Jude, MD

From the Laboratoire d'Hématologie (D.C., B.J.), Service de Cardiologie et Hémodynamique (C.B., E.P.M.), Service des Soins Intensifs (P.A.), Service Commun d'Imagerie Interventionnelle (T.L.T., I.S., T.M.), Centre Hospitalier Régional Universitaire and Faculté de Médecine, Lille, France, and Section of Cardiovascular Medicine (M.D.E.), Yale University, New Haven, Conn.

Correspondence to Brigitte Jude, MD, Laboratoire d'Hématologie, Hôpital Cardiologique, Boulevard du Professeur J Leclercq, 59037 Lille Cedex, France. E-mail b.jude{at}chru_lille.fr

Background—There is evidence that tissue factor (TF) is a major contributor to the thrombogenicity of a ruptured atherosclerotic plaque. Nitric oxide (NO) has antiatherogenic and antithrombotic properties. We investigated whether L-arginine (L-arg), the endogenous precursor of NO, might affect the ability of monocytes to produce TF.

Methods and Results—We studied TF expression in 18 rabbits with atherosclerosis induced by bilateral iliac damage and 10 weeks of a 2% cholesterol diet. Six weeks after the initiation of the diet, an angioplasty was performed. After angioplasty, the surviving rabbits (n=15) were randomized to receive L-arg (2.25%) supplementation in drinking water (L-arg group, n=8) or no treatment (untreated group, n=7). TF expression was evaluated 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 induction of atherosclerotic lesions (87±15 versus 70±12 mU of TF/1000 monocytes, P=NS). Endotoxin-stimulated TF activity increased significantly 4 weeks after angioplasty (138±22 versus 70±12 mU of TF/1000 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 that angioplasty-induced plaque rupture is associated with a marked increase 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 response.

Key Words: tissue factor • monocytes • nitric oxide • atherosclerosis

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