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         headline:Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis
         description: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. 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.
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      headline:Guggulsterone, an anti-inflammatory phytosterol, inhibits tissue factor and arterial thrombosis
      description: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. 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.
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            type:Organization
      name:Caroline E. Gebhard
      affiliation:
            name:University of Zurich
            address:
               name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
      name:Alexander Akhmedov
      affiliation:
            name:University of Zurich
            address:
               name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
      name:Alexander Breitenstein
      affiliation:
            name:University of Zurich
            address:
               name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University Hospital Zurich
            address:
               name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
      name:Giovanni G. Camici
      affiliation:
            name:University of Zurich
            address:
               name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
      name:Erik W. Holy
      affiliation:
            name:University of Zurich
            address:
               name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University Hospital Zurich
            address:
               name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
      name:Thomas F. Lüscher
      affiliation:
            name:University of Zurich
            address:
               name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University Hospital Zurich
            address:
               name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
      name:Felix C. Tanner
      affiliation:
            name:University of Zurich
            address:
               name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
            name:University Hospital Zurich
            address:
               name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
      name:Cardiovascular Research, Institute of Physiology, University of Zurich, Zürich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zürich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zürich, Switzerland
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