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. 2010 Apr 1;5(2):209-219.
doi: 10.2217/clp.10.11.

Thromboxane and the thromboxane receptor in cardiovascular disease

Emer M Smyth  1
Affiliations

Thromboxane and the thromboxane receptor in cardiovascular disease

Emer M Smyth. Clin Lipidol. .

Abstract

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.

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Figures

Figure 1
Figure 1. Simplified scheme of TXA2 generation and TP signaling
Platelet COX-1-dependent metabolism of AA is the dominant source of TXA2. Activation of the TP (agonists shown in pale blue boxes) induces biological effects that drive CVD. Multiple signaling pathways have been described for TP but the primary ones associated with TXA2 biological function are activation of RhoA or PLCβ. ROS-dependent upregulation of TP expression may increase TXA2/isoprostane responses during CVD/oxidant stress. TP signaling is limited by its desensitization and downregulation. AA: Arachidonic acid; EC: Endothelial cell; PGH2: Prostaglandin H2; ROS: Reactive oxygen species; TP: TXA2 receptor; TXA2: Thromboxane A2; TXAS: TCA2 synthase.
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