Role of Thromboxane Receptor in C-Reactive Protein–Induced Thrombosis
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.
- Received March 30, 2012.
- Accepted July 19, 2012.
- © 2012 American Heart Association, Inc.