Role of thromboxane receptor in C-reactive protein-induced thrombosis.

Etty Grad, Rachel M Pachino, Garret A FitzGerald, Haim D Danenberg

Cardiovascular Research Center, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel.

Arteriosclerosis, thrombosis, and vascular biology 2012 Oct

filter terms:

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. 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). 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.

Citation

Etty Grad, Rachel M Pachino, Garret A FitzGerald, Haim D Danenberg. Role of thromboxane receptor in C-reactive protein-induced thrombosis. Arteriosclerosis, thrombosis, and vascular biology. 2012 Oct;32(10):2468-74