Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis
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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.
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.
- Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis
Basic Research in Cardiology
Volume 104, Issue 3 , pp 285-294
- Cover Date
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- arterial thrombosis
- photochemical injury
- tissue factor
- Industry Sectors
- Author Affiliations
- 1. Cardiovascular Research, Institute of Physiology, University of Zurich, Winterthurerstraße 190, 8057, Zürich, Switzerland
- 2. Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
- 3. Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland