- Paper Report
- Open Access
PGI2 and TXA2in vascular injury
- Jose L Pablos1
© Biomed Central Ltd 2002
- Received: 9 May 2002
- Accepted: 5 July 2002
- Published: 11 July 2002
- cardiovascular disease
Cyclooxygenases participate in the pathogenesis of atherothrombotic lesions by two opposing mechanisms. Platelet cyclooxygenase-1 (COX-1) participates in the synthesis of thromboxane A2 (TxA2), a potent vasoconstrictor and platelet activator, and endothelial cyclooxygenase-2 (COX-2) mediates the synthesis of prostacyclin (PGI2), a vasodilator and platelet inhibitor. Nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin exert differential effects on platelet-endothelium interactions that are dependent upon their relative capacity to inhibit COX-1 and COX-2 isoenzymes. Potent and sustained inhibition of COX-1 by low dose aspirin provides efficient anti-thrombotic prophylaxis. Different NSAIDs can induce transient and variable inhibition of COX-1-dependent TxA2 synthesis, and all NSAIDs and COX-2 selective drugs inhibit COX-2 dependent PGI2 synthesis, but the clinical relevance of both effects is still unclear. These authors explored the role of TxA2/PGI2 balance in the response to vascular injury using TxA2 and PGI2 receptor knockout mice.
Catheter-induced vascular injury was enhanced in mice genetically deficient in the PGI2 receptor, whereas it was depressed in those mice genetically deficient in the TxA2 receptor or treated with a TxA2 receptor antagonist. The augmented response to vascular injury was abolished in mice deficient in both receptors.
Carotid-induced injury, histomorphometric analyses.