(Circulation. 2001;103:207.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
PPAR
Agonists Inhibit Tissue Factor Expression in Human Monocytes and Macrophages
From the Département d’Athérosclérose, U.325 INSERM, Institut Pasteur de Lille, and the Faculté de Pharmacie, Université de Lille II (B.P.N., G.C., J.-C.F., P.D., B.S.), and the Laboratoire d’ Hématologie, Hôpital Cardiologique (D.C., C.Z., B.J.), Lille, France. The first 2 authors contributed equally to this article.
Correspondence to Brigitte Jude, Laboratoire d’Hématologie, Hôpital Cardiologique, Boulevard du Professeur J. Leclercq, 59037 Lille CEDEX, France. E-mail b-jude{at}chru-lille.fr
Background—Monocytic
tissue factor (TF) expression may contribute to thrombogenicity
associated with plaque rupture and may propagate thrombus formation at
the site of vascular lesions. Induction of monocytic TF expression by
endotoxin is mediated by the activation of transcription factors such
as AP-1 and NF-
B. Both these signaling pathways are modulated by
peroxisome proliferator–activated receptor-
(PPAR). Therefore,
we have studied the effects of fibrates and other PPAR agonists on
the expression of TF.
Methods and Results—We
show that PPAR protein, like primary human monocytes, is also
expressed in the human monocytic THP-1 cell line. Fenofibric acid,
WY14643, and GW2331 inhibited TF mRNA upregulation after stimulation of
THP-1 cells with lipopolysaccharide or interleukin-1ß. In primary
human monocytes and macrophages, the lipopolysaccharide- or
interleukin-1ß–mediated induction of TF activity was also inhibited
by fenofibric acid, WY14643, or GW2331.
Conclusions—These data
indicate that activation of PPAR results in the downregulation of
the TF gene. Our results suggest a novel role for PPAR in the
control of atherosclerotic plaque thrombogenicity through its effects
on TF expression in monocytes and
macrophages.
Key Words: tissue factor • lipopolysaccharide • receptors • monocytes • fibrates
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