Tissue factor modulates the thrombogenicity of human atherosclerotic plaques

Vincenzo Toschi, Richard Gallo, Maddalena Lettino, John T. Fallon, S. David Gertz, Antonio Fernández-Ortiz, James H. Chesebro, Lina Badimon, Yale Nemerson, Valentin Fuster, Juan J. Badimon

Research output: Contribution to journalArticlepeer-review

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 111In-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 semi-quantitatively 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.

Original languageEnglish
Pages (from-to)594-599
Number of pages6
JournalCirculation
Volume95
Issue number3
Publication statusPublished - 1997

Keywords

  • atherosclerosis
  • plaque
  • platelets
  • thrombosis
  • tissue factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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