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

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Abstract

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.

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Acknowledgments

This study was supported by the Swiss National Science Foundation (grant no. 3200B0-113328/1 to FCT and grant no. 3100-068118.02/1 to TFL), Bonizzi-Theler Foundation, Velux Foundation, Wolfermann Nägeli Foundation, and the Swiss Heart Foundation. The authors thank Helen Greutert for expert technical support.

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Authors and Affiliations

  1. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland

    Catherine Gebhard MD, Simon F. Stämpfli MD, Caroline E. Gebhard, Alexander Akhmedov PhD, Alexander Breitenstein MD, Giovanni G. Camici PhD, Erik W. Holy MD, Thomas F. Lüscher MD & Felix C. Tanner MD

  2. Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland

    Catherine Gebhard MD, Simon F. Stämpfli MD, Caroline E. Gebhard, Alexander Akhmedov PhD, Alexander Breitenstein MD, Giovanni G. Camici PhD, Erik W. Holy MD, Thomas F. Lüscher MD & Felix C. Tanner MD

  3. Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland

    Catherine Gebhard MD, Simon F. Stämpfli MD, Alexander Breitenstein MD, Erik W. Holy MD, Thomas F. Lüscher MD & Felix C. Tanner MD

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  1. Catherine Gebhard MD
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  2. Simon F. Stämpfli MD
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Correspondence to Felix C. Tanner MD.

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Gebhard, C., Stämpfli, S.F., Gebhard, C.E. et al. Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis. Basic Res Cardiol 104, 285–294 (2009). https://doi.org/10.1007/s00395-008-0757-5

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  • DOI: https://doi.org/10.1007/s00395-008-0757-5

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