Thromboxane

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Thromboxane is a member of the lipid family known as eikosanoid. Two major thromboxane are thromboxane A2 and thromboxane B2. The distinguishing feature of thromboxanes is a 6 membered ring of ether members.

Thromboxane is named for its role in the formation of blood clots (thrombosis).

Video Thromboxane

Production

Thromboxane-A synthase, an enzyme found in platelets, converts the arachidonic acid of prostaglandin H ₂ into thromboxane.

Maps Thromboxane

Mechanism

Thromboxane acts by binding to one of the thromboxane receptors, G-protein-coupled receptor coupled with G protein G _q .

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Function

Thromboxane is a vasoconstrictor and potential hypertension agent, and facilitates platelet aggregation.

This is the homeostatic balance in the circulatory system with prostacyclin, related compounds. The mechanism of thromboxanes secretion from platelets remains unclear. They act in the formation of blood clots and reduce blood flow to the blood clot.

If a plaque cap is vulnerable to eroding or rupturing, as in myocardial infarction, platelets attach to the damaged vessel lining and to each other within seconds and form a plug. These "Sticky platelets" secrete several chemicals, including A2 thromboxane which stimulates vasoconstriction, reducing blood flow in the site.

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The role of A2 in platelet aggregation

Thromboxane A ₂ (TXA ₂ ), produced by activated platelets, has prothrombotic properties, stimulates new platelet activation as well as enhances platelet aggregation.

Platelet aggregation is achieved by mediating GP IIb/IIIa GP glycoprotein complex expression in platelet cell membrane. Circulating fibrinogen binds these receptors to adjacent platelets, further strengthening the clot.

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Pathology

It is believed that vasoconstriction caused by thromboxanes plays a role in Prinzmetal angina. Omega-3 fatty acids are metabolized to produce higher levels of TxA, ₃ relatively less potent than TxA ₂ and PGI ₃ ; therefore, there is a shift in the balance leading to inhibition of vasoconstriction and platelet aggregation. It is believed that this shift in equilibrium decreases the incidence of myocardial infarction (heart attack) and stroke. The vasoconstriction and, possibly, the various proinflammatory effects given by TxA on microvasculature tissue, is a possible reason why TxA is pathogenic in various diseases, such as ischemic-reperfusion injury, hepatic inflammatory processes, acute hepatotoxicity, etc. TxB2, the stable degradation product of TxA2, plays a role in acute hepatoccales induced by acetaminophen.

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Inhibitors

Thromboxane inhibitors are widely classified as one that inhibits thromboxane synthesis, or which inhibits its target effects.

Thromboxane synthesis inhibitors, in turn, can be classified as to which steps in their synthesis are inhibited:

• A widely used drug aspirin acts by inhibiting the ability of COX enzymes to synthesize thromboxane precursors in platelets. Low-dose aspirin and long-term block using thromboxane block A ₂ in platelets, resulting in inhibitory effects on platelet aggregation. These anticoagulant properties make aspirin useful for reducing the incidence of heart attacks. 40 mg of aspirin a day was able to inhibit most of the acute provoked A ₂ acute thromboxane, with slightly affected prostaglandin I2 synthesis; however, a higher aspirin dose is required to achieve further inhibition.
• Thromboxane synthase inhibitors inhibit the final enzyme (thromboxane synthase) in thromboxane synthesis. Ifetroban is a potent and selective thromboxane receptor antagonist. Dipyridamole is also hostile to these receptors, but it has many other mechanisms of antiplatelet activity as well.
High doses of nitroxen can induce near-perfect thromboxy platelet suppression along dosing intervals and do not appear to increase the risk of cardiovascular disease (CVD), whereas other high doses of NSAID (non-steroid-anti-inflammatory) NSAID regimens have only a temporary effect on platelet COX- 1 and have been found to be associated "with a small but definite vascular danger".

Inhibitors of thromboxane target effects are thromboxane receptor antagonists, including terutroban.

Picotamide has activity both as a thromboxane synthase inhibitor and as a thromboxane receptor antagonist.

Ridogrel is another example.

src: www.onlinejacc.org

References

src: circ.ahajournals.org

External links

• Thromboxanes at the US National Medical Library Title of Medical Subject (MeSH)

Source of the article : Wikipedia