Tissue Factor Modulates the Thrombogenicity of Human Atherosclerotic Plaques

Author:

Toschi Vincenzo1,Gallo Richard1,Lettino Maddalena1,Fallon John T.1,Gertz S. David1,Ferna´ndez-Ortiz Antonio1,Chesebro James H.1,Badimon Lina1,Nemerson Yale1,Fuster Valentin1,Badimon Juan J.1

Affiliation:

1. the Cardiovascular Biology Research Laboratory, The Cardiovascular Institute, Mount Sinai School of Medicine, New York, NY; Department of Anatomy and Embryology (S.D.G.), The Hebrew University–Hadassah Medical, Jerusalem, Israel; Servicio de Cardiologia (A.F.-O.), Hospital San Carlos Madrid, Spain; and Cardiovascular Research Center (L.B.), CSIC-Hospital Santa Cruz y San Pablo–UAB, Barcelona, Spain.

Abstract

Background The thrombogenicity of a disrupted atherosclerotic lesion is dependent on the nature and extent of the plaque components exposed to flowing blood together with local rheology and a variety of systemic factors. We previously reported on the different thrombogenicity of the various types of human atherosclerotic lesions when exposed to flowing blood in a well-characterized perfusion system. This study examines the role of tissue factor in the thrombogenicity of different types of atherosclerotic plaques and their components. Methods and Results Fifty human arterial segments (5 foam cell–rich, 9 collagen-rich, and 10 lipid-rich atherosclerotic lesions and 26 normal, nonatherosclerotic segments) were exposed to heparinized blood at high shear rate conditions in the Badimon perfusion chamber. The thrombogenicity of the arterial specimens was assessed by 111 In-labeled platelets. After perfusion, specimens were stained for tissue factor by use of an in situ binding assay for factor VIIa. Tissue factor in specimens was semiquantitatively assessed on a scale of 0 to 3. Platelet deposition on the lipid-rich atheromatous core was significantly higher than on all other substrates ( P =.0002). The lipid-rich core also exhibited the most intense tissue factor staining (3±0.1 arbitrary units) compared with other arterial components. Comparison of all specimens showed a positive correlation between quantitative platelet deposition and tissue factor staining score ( r =.35, P <.01). Conclusions Our results show that tissue factor is present in lipid-rich human atherosclerotic plaques and suggest that it is an important determinant of the thrombogenicity of human atherosclerotic lesions after spontaneous or mechanical plaque disruption.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Physiology (medical),Cardiology and Cardiovascular Medicine

Reference44 articles.

1. Badimon JJ Fuster V Chesebro JH Badimon L. Coronary atherosclerosis: a multifactorial disease. Circulation . 1993;87(suppl II):II-3-II-16.

2. Plaque rupture with severe pre-existing stenosis precipitating coronary thrombosis. Characteristics of coronary atherosclerotic plaques underlying fatal occlusive thrombi.

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