Local inhibition of tissue factor reduces the thrombogenicity of disrupted human atherosclerotic plaques. Effects of tissue factor pathway inhibitor on plaque thrombogenicity under flow conditions

Juan Jose Badimon, Maddalena Lettino, Vincenzo Toschi, Valentin Fuster, Maria Berrozpe, James H. Chesebro, Lina Badimon

Research output: Contribution to journalArticle

Abstract

Background - Plaque disruption and subsequent thrombus formation lead to acute coronary syndromes and progression of atherosclerotic disease. Tissue factor (TF) appears to mediate plaque thrombogenicity. Tissue factor pathway inhibitor (TFPI) is the major physiological inhibitor of TF. This study analyzes the role of TF on thrombogenicity of disrupted human atherosclerotic plaques and the therapeutic possibilities of its specific inhibition. Methods and Results - Human atherosclerotic and normal arterial segments were exposed to heparinized blood at flow conditions modeling medium-grade coronary stenosis in the Badimon perfusion chamber. The antithrombotic effects of the specific inhibition of plaque TF was assessed by reduction in the deposition of radiolabeled platelets and fibrin(ogen) and immunohistochemical analysis of perfused arteries. TF activity was inhibited by both recombinant TFPI and a polyclonal antibody against human TF. Human lipid-rich plaques were more thrombogenic than less advanced atherosclerotic plaques. Specific inhibition of TF activity reduced plaque thrombogenicity, inhibiting both platelet and fibrin(ogen) deposition (580 versus 194 platelets x 106/cm2; P12 molecules of Fg/cm2; P

Original languageEnglish
Pages (from-to)1780-1787
Number of pages8
JournalCirculation
Volume99
Issue number14
Publication statusPublished - Apr 13 1999

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Keywords

  • Atherosclerosis
  • Coronary disease
  • TFPI
  • Thrombosis
  • Tissue factor

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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