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(Circulation. 2000;101:2000.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Basic Fibroblast Growth Factor Increases Tissue Factor Expression in Circulating Monocytes and in Vascular Wall

Delphine Corseaux, PhD; Thibaud Meurice, MD; Isabelle Six, PhD; Lucia Rugeri, MD; Michael D. Ezekowitz, MD, PhD; Philippe Rouvier, MD; Régis Bordet, MD; Christophe Bauters, MD; Brigitte Jude, MD

From the Laboratoire d’Hématologie (D.C., L.R., B.J.), Service de Cardiologie et Hémodynamique (T.M., C.B.), Service de Pharmacologie (R.B.), Service Commun d’Imagerie Interventionnelle (I.S.), and Laboratoire d’Anatomie et de Cytologie Pathologiques C (P.R.), Centre Hospitalier Régional Universitaire and Faculté de Médecine, Lille, France; and Section of Cardiovascular Medicine, Yale University, New Haven, Conn (M.D.E.).

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—Basic fibroblast growth factor (bFGF) promotes vascular repair and angiogenesis and can induce in vitro tissue factor (TF), a potent agent initiating thrombogenesis, which probably plays a role in angiogenesis. We investigated whether bFGF administration induced TF expression by monocytes and vascular cells.

Methods and Results—We studied TF expression in normally fed (n=16) and cholesterol-fed (2% for 6 weeks, n=16) rabbits. Animals were then randomized to receive intravenous bFGF (2.5 µg twice weekly for 3 weeks) or saline injections. TF expression was evaluated in mononuclear cells from arterial blood and in aortic sections by an immunohistochemical assay using a monoclonal anti-rabbit TF antibody (activator protein 1). Monocyte TF expression was increased by bFGF administration in both normal and hypercholesterolemic rabbits (129±45 versus 19±3 mU TF/1000 monocytes, P<0.05, and 31±12 versus 7±1 mU TF/1000 monocytes, P<0.005, respectively) and was further increased by stimulation of monocytes by endotoxin in vitro. TF expression was lower in hypercholesterolemic rabbits than in normal rabbits. In the media of the vascular wall, bFGF induced strong TF expression in normal rabbits and only weak TF expression in hypercholesterolemic ones.

Conclusions—This study demonstrates that systemic administration of bFGF induces an impressive increase of TF expression in circulating monocytes and in the vascular wall in normal and to a lower extent in hypercholesterolemic rabbits. The significance of this observation in terms of inducing thrombosis in vivo needs clarification.

Key Words: growth substances • leukocytes • vessels

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