Thromboxane A2 (TXA2) is a type of
thromboxane that is produced by activated
platelets during
hemostasis and has prothrombotic properties: it stimulates activation of new platelets as well as increases platelet aggregation. This is achieved by activating the
thromboxane receptor, which results in platelet-shape change, inside-out activation of
integrins, and
degranulation.[1] Circulating
fibrinogen binds these receptors on adjacent platelets, further strengthening the
clot. Thromboxane A2 is also a known
vasoconstrictor[2][3][4][5] and is especially important during tissue injury and inflammation. It is also regarded as responsible for
Prinzmetal's angina.
Receptors that mediate TXA2 actions are
thromboxane A2 receptors. The human TXA2 receptor (TP) is a typical G protein-coupled receptor (GPCR) with seven transmembrane segments. In humans, two TP receptor splice variants – TPα and TPβ – have so far been cloned.
Synthesis and breakdown
TXA2 is generated from
prostaglandin H2 by
thromboxane-A synthase in a metabolic reaction which generates approximately equal amounts of 12-Hydroxyheptadecatrienoic acid (12-HHT).
Aspirin irreversibly inhibits platelet
cyclooxygenase 1 preventing the formation of prostaglandin H2, and therefore thromboxane A2. Contrastly, TxA2 vascular tissue synthesis is stimulated by angiotensin II which promotes cyclooxygenase I's metabolism of arachidonic acid. An angiotensin II dependent pathway also induces hypertension and interacts with TxA2 receptors.[6]
TXA2 is very unstable in aqueous solution, since it is hydrated within about 30 seconds to the biologically inactive
thromboxane B2. 12-HHT, while once thought to be an inactive byproduct of TXA2 synthesis, has recently been shown to have a range of potentially important actions, some of which relate to the actions of TXA2 (see
12-Hydroxyheptadecatrienoic acid).[7] Due to its very short half life, TXA2 primarily functions as an autocrine or paracrine mediator in the nearby tissues surrounding its site of production. Most work in the field of TXA2 is done instead with synthetic analogs such as
U46619 and
I-BOP.[8] In human studies,
11-dehydrothromboxane B2 levels are used to indirectly measure TXA2 production.[9][10]