PGI2 and TXA2in vascular injury
- Jose L Pablos1
© Biomed Central Ltd 2002
Received: 9 May 2002
Accepted: 5 July 2002
Published: 11 July 2002
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.
The results of Cheng et al. are consistent with the well known role of TxA2 in vascular disease and demonstrate a role in counterbalancing TxA2 platelet activation for PGI2 synthesized in response to vascular injury. However, the authors' extrapolation regarding the clinical use of NSAIDs versus COX-2 selective inhibitors is not clear because most NSAIDs lack the potent inhibition and anti-platelet effect provided by aspirin. These data in knockout mice remind us of the need to ensure anti-platelet prophylaxis in patients with cardiovascular disease, particularly before using either NSAIDs or COX inhibitors, but further studies on the potential clinical effects of PGI2 inhibition by both types of drugs are still warranted.
Carotid-induced injury, histomorphometric analyses.