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