Concept

Prostacyclin

Summary
Prostacyclin (also called prostaglandin I2 or PGI2) is a prostaglandin member of the eicosanoid family of lipid molecules. It inhibits platelet activation and is also an effective vasodilator. When used as a drug, it is also known as epoprostenol. The terms are sometimes used interchangeably. Prostacyclin (PGI2) chiefly prevents formation of the platelet plug involved in primary hemostasis (a part of blood clot formation). It does this by inhibiting platelet activation. It is also an effective vasodilator. Prostacyclin's interactions contrast with those of thromboxane (TXA2), another eicosanoid. Both molecules are derived from arachidonic acid, and work together with opposite platelet aggregatory effects. These strongly suggest a mechanism of cardiovascular homeostasis between these two hormones in relation to vascular damage. It is used to treat pulmonary arterial hypertension (PAH), pulmonary fibrosis, as well as atherosclerosis. Specifically, epoprostenol is given to patients with class III or class IV PAH. Prostacyclin, which has a half-life of 42 seconds, is broken down into 6-keto-PGF1, which is a much weaker vasodilator. A way to stabilize prostacyclin in its active form, especially during drug delivery, is to prepare prostacyclin in alkaline buffer. Even at physiological pH, prostacyclin can rapidly form the inactive hydration product 6-keto-prostaglandin F1α. {| class=wikitable !colspan=2|Prostacyclin effect !Mechanism !Cellular response |- | rowspan=3|Classicalfunctions | Vessel tone |↑cAMP, ↓ET-1↓Ca2+, ↑K+ |↓SMC proliferation↑Vasodilation |- | Antiproliferative |↑cAMP ↑PPARgamma |↓Fibroblast growth↑Apoptosis |- | Antithrombotic |↓Thromboxane-A2↓PDGF |↓Platelet aggregation↓Platelet adherence to vessel wall |- | rowspan=2|Novelfunctions | Antiinflammatory |↓IL-1, IL-6↑IL-10 |↓Proinflammatory cytokines↑Antiinflammatory cytokines |- | Antimitogenic |↓VEGF↓TGF-β |↓Angiogenesis↑ECM remodeling |} As mentioned above, prostacyclin (PGI2) is released by healthy endothelial cells and performs its function through a paracrine signaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells.
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