title: Role of thromboxane receptor in C-reactive protein-induced thrombosis.
abstract: OBJECTIVE
  Thromboxane A(2) and prostacyclin are thromboregulatory prostaglandins. The inflammatory C-reactive protein (CRP) promotes thrombosis after vascular injury, presumably via potentiation of thromboxane activity. Using a genetic approach, we investigated the role of thromboxane receptor (TP) pathway in CRP-induced thrombosis.
  
  
  RESULTS
  Four genetically engineered mice strains were used: C57BL/6 wild-type, human CRP transgenic (CRPtg), thromboxane receptor-deficient (Tp(-/-)), and CRPtgTp(-/-) mice. CRP and TP expression were correlated, and suppression of CRP expression using small interfering RNA/CRP led to reduction in TP expression. Platelet-endothelial adherence was increased in CRPtg and suppressed in CRPtgTP(-/-)and CRPtg cells that were suppressed with TP small interfering RNA. TP deficiency in both platelets and endothelial cells was synergistic in affecting platelet-endothelial interactions. Time until arterial occlusion, measured after photochemical injury, was significantly shorter in CRPtg and prolonged in CRPtgTp(-/-) compared with controls (n=10-15, 35±3.4, 136±13.8, and 67±8.9 minutes, respectively; P<0.05).
  
  
  CONCLUSIONS
  TP pathway is of major importance in CRP-induced thrombosis. The expression of TP is increased in CRPtg endothelial cells, and its blockade significantly suppresses the prothrombotic effect of CRP.
authors.affiliation: Cardiovascular Research Center, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel.
authors.forename: Etty
authors.initials: E
authors.lastname: Grad
authors.forename: Rachel M
authors.initials: RM
authors.lastname: Pachino
authors.forename: Garret A
authors.initials: GA
authors.lastname: FitzGerald
authors.forename: Haim D
authors.initials: HD
authors.lastname: Danenberg
mesh_terms: D000328:Adult; D000818:Animals; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology; D002097:C-Reactive Protein / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002448:Cell Adhesion / Q000502:physiology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D034741:RNA, Small Interfering / Q000494:pharmacology; D017482:Receptors, Thromboxane / Q000172:deficiency / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013927:Thrombosis / Q000473:pathology / Q000503:physiopathology*; D014162:Transfection
chemical_list: D034741:RNA, Small Interfering; D017482:Receptors, Thromboxane; D002097:C-Reactive Protein