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Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis

Gebhard, Catherine ; Stämpfli, Simon ; Gebhard, Caroline ; Akhmedov, Alexander ; Breitenstein, Alexander ; Camici, Giovanni ; Holy, Erik ; Lüscher, Thomas ; Tanner, Felix

In: Basic Research in Cardiology, 2009, vol. 104, no. 3, p. 285-294

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    Titre
    • Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis
    Auteur
    • Gebhard, Catherine. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    • Stämpfli, Simon. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    • Gebhard, Caroline. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    • Akhmedov, Alexander. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    • Breitenstein, Alexander. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    • Camici, Giovanni. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    • Holy, Erik. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    • Lüscher, Thomas. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    • Tanner, Felix. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Basic Research in Cardiology, 2009, vol. 104, no. 3, p. 285-294. Steinkopff-Verlag; www.steinkopff.springer.de
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:311356
    Summary
    Background: The phytosterol guggulsterone is a potent anti-inflammatory mediator with less side effects than classic steroids. This study assesses the impact of guggulsterone on tissue factor (TF) expression and thrombus formation. Methods and results: Guggulsterone inhibited TNF-α-induced endothelial TF protein expression and surface activity in a concentration-dependent manner; in contrast, dexamethasone did not affect TNF-α-induced TF expression. Guggulsterone enhanced endothelial tissue factor pathway inhibitor and impaired plasminogen activator inhibitor-1 as well as vascular cell adhesion molecule-1 protein. Real-time polymerase chain reaction revealed that guggulsterone inhibited TNF-α-induced TF mRNA expression; moreover, it impaired activation of the MAP kinases JNK and p38, while that of ERK remained unaffected. In vivo, guggulsterone inhibited TF activity and photochemical injury induced thrombotic occlusion of mouse carotid artery. Guggulsterone also inhibited TF expression, proliferation, and migration of vascular smooth muscle cells in a concentration-dependent manner. Conclusions: Guggulsterone inhibits TF expression in vascular cells as well as thrombus formation in vivo; moreover, it impairs vascular smooth muscle cell activation. Hence, this phytosterol offers novel therapeutic options, in particular in inflammatory diseases associated with an increased risk of thrombosis