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.

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.

• Authors: Etty Grad, Rachel M Pachino, Garret A FitzGerald, Haim D Danenberg
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 32 Issue 10 Pg. 2468-74 (Oct 2012) ISSN: 1524-4636 [Electronic] United States
• PMID: 22879580 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• RNA, Small Interfering
• Receptors, Thromboxane
• C-Reactive Protein

Topics

• Adult
• Animals
• Blood Platelets (pathology, physiology)
• C-Reactive Protein (deficiency, genetics, physiology)
• Cell Adhesion (physiology)
• Disease Models, Animal
• Endothelium, Vascular (pathology, physiopathology)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mice, Transgenic
• RNA, Small Interfering (pharmacology)
• Receptors, Thromboxane (deficiency, drug effects, physiology)
• Signal Transduction (physiology)
• Thrombosis (pathology, physiopathology)
• Transfection