Thromboxane and the thromboxane receptor in cardiovascular disease.
Thromboxane A(2) (TXA(2)), the primary product of COX-1-dependent metabolism of arachidonic acid, mediates its biological actions through the TXA(2) receptor, termed the TP. Irreversible inhibition of platelet COX-1-derived TXA(2) with low-dose aspirin affords protection against primary and secondary vascular thrombotic events, underscoring the central role of TXA(2) as a platelet agonist in cardiovascular disease. The limitations associated with aspirin use include significant gastrointestinal toxicity, bleeding complications, potential interindividual response variability and poor efficacy in some disease states. This, together with the broad role of TXA(2) in cardiovascular disease beyond the platelet, has refocused interest towards additional TXA(2)-associated drug targets, in particular TXA(2) synthase and the TP. The superiority of these agents over low-dose aspirin, in terms of clinical efficacy, tolerability and commercial viability, remain open questions that are the focus of ongoing research.
Smyth
Emer M
EM
Institute for Translation Medicine & Therapeutics, University of Pennsylvania, 421 Curie Blvd, 808 BRB 2/3, Philadelphia, PA 19104, USA Tel.: +1 215 573 2323 emsmyth@mail.med.upenn.edu.