| First Author | Grad E | Year | 2012 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 32 |
| Issue | 10 | Pages | 2468-74 |
| PubMed ID | 22879580 | Mgi Jnum | J:201477 |
| Mgi Id | MGI:5514197 | Doi | 10.1161/ATVBAHA.112.256073 |
| Citation | Grad E, et al. (2012) Role of thromboxane receptor in C-reactive protein-induced thrombosis. Arterioscler Thromb Vasc Biol 32(10):2468-74 |
| abstractText | 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. 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). 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. |
