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-I1 derived TXA2 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 inter-individual 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.