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on September 22, 2003

Circulation. 2003
Published online before print September 22, 2003, doi: 10.1161/01.CIR.0000089370.84709.51
A more recent version of this article appeared on October 7, 2003
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Submitted on April 8, 2003
Revised on June 12, 2003
Accepted on June 13, 2003

Dietary Lipid Lowering Modifies Plaque Phenotype in Rabbit Atheroma After Angioplasty. A Potential Role of Tissue Factor

Emmanuelle Jeanpierre ; , Thierry Le Tourneau MD, PhD, Isabelle Six PhD, Christophe Zawadzki , Eric Van Belle MD, PhD, Michael D. Ezekowitz MD, PhD, Régis Bordet MD, PhD, Sophie Susen MD, Brigitte Jude MD, PhD*, and Delphine Corseaux PhD

From Equipe d'accueil 2693 (E.J., T.L.T., E.V.B., S.S., C.Z., B.J., D.C.) and 1046 (I.S., R.B.), IFR 114, University of Lille II and Centre Hospitalier Régional Universitaire de Lille, France, and Section of Cardiovascular Medicine, Yale University, New Haven, Conn (M.D.E.).

* To whom correspondence should be addressed. E-mail: b-jude{at}chru-lille.fr.

Background--Tissue factor (TF), the main initiator of blood coagulation, is involved in cellular migration and angiogenesis processes. TF is expressed strongly in lipid-rich plaques and probably plays an important role in the thrombotic complications of plaque rupture. This study analyzes the effect of dietary lipid lowering on TF expression and cellular modifications in angioplasty-induced rabbit plaque rupture.

Methods and Results--After experimental plaque rupture by balloon angioplasty in atheromatous rabbits, animals were assigned a 0.2% or a 2% cholesterol diet, and the TF content of arterial wall and the associated histological modifications were analyzed after 4 weeks. Early effects of lipid lowering were observed: The increase of TF expression in the vascular wall was stronger in the 2% than in the 0.2% cholesterol diet group (iliac arteries: 1226±308 versus 72±29 mU TF/g artery, P<0.005). Immunohistochemistry indicated that TF expression was associated with sprout of neovessels, which was more pronounced in the 2% than in the 0.2% cholesterol group.

Conclusions--This study shows that dietary lipid lowering decreases the thrombotic potential of ruptured atherosclerotic plaques through TF decrease. Moreover, high TF expression is associated with marked angiogenesis in the vascular wall, which is reduced by lipid lowering. These results provide further arguments for strong dietary lipid lowering to reduce plaque instability and thrombogenicity.


Key words: tissue factor • atherosclerosis • angioplasty • lipids




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