Role of thromboxane receptor in c-reactive protein-induced thrombosis

Etty Grad, Rachel M. Pachino, Garret A. Fitzgerald, Haim D. Danenberg

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


OBJECTIVE-: Thromboxane A2 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. METHODS AND 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). CONCLUSION-: 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.

Original languageEnglish
Pages (from-to)2468-2474
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number10
StatePublished - Oct 2012
Externally publishedYes


  • C-reactive protein
  • endothelium
  • platelets
  • thrombosis
  • thromboxane receptor


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