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Topics {✒️}

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         headline:PDGF-CC induces tissue factor expression: role of PDGF receptor α/β
         description:Tissue factor (TF) is the principal trigger of the coagulation cascade and involved in arterial thrombus formation. Platelet-derived growth factor CC (PDGF-CC) is a recently discovered member of the PDGF family released upon platelet activation. This study assesses the impact of PDGF-CC on TF expression in human cells. PDGF-CC concentration-dependently induced TF expression by 2.5-fold in THP-1 cells, by 2.0-fold in human peripheral blood monocytes, by 1.4-fold in vascular smooth muscle cells, and by 2.6-fold in microvascular endothelial cells, but did not affect TF expression in aortic endothelial cells. A similar pattern was observed with PDGF-BB. In contrast, PDGF-AA did not alter TF expression in THP-1 cells. TF whole cell activity was induced following stimulation with PDGF-BB and PDGF-CC in THP-1 cells. Real-time polymerase chain reaction revealed that PDGF-CC induced TF mRNA. PDGF-CC transiently activated p42/44 MAP kinase [extracellular signal-regulated kinase (ERK)], while phosphorylation of the MAP kinases c-Jun NH2-terminal kinase (JNK) and p38 remained unaffected. PD98059, a specific inhibitor of ERK phosphorylation, but not the p38 inhibitor SB203580 or the JNK inhibitor SP600125 prevented PDGF-CC induced TF expression in a concentration-dependent manner. The effect of PDGF-CC was antagonized by both PDGF receptor α and PDGF receptor β neutralizing antibodies; in contrast, PDGF-BB was only inhibited by PDGF receptor β blocking antibody. PDGF receptor α and PDGF receptor β inhibition prevented PDGF-CC-induced ERK phosphorylation. PDGF-CC induces TF expression via activation of α/β receptor heterodimers and an ERK-dependent signal transduction pathway.
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      headline:PDGF-CC induces tissue factor expression: role of PDGF receptor α/β
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         PDGF
         Monocytes
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         Arterial thrombosis
         Cardiology
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               type:PostalAddress
            type:Organization
            name:University of Zurich
            address:
               name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
            name:University Hospital Zurich
            address:
               name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
               type:PostalAddress
            type:Organization
      email:[email protected]
PostalAddress:
      name:Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
      name:Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
      name:Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
      name:Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
      name:Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
      name:Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
      name:Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
      name:Cardiovascular Research, Physiology Institute, University of Zurich, Zurich, Switzerland
      name:Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
      name:Cardiology, Cardiovascular Center, University Hospital Zurich, Zurich, Switzerland
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