PGI2

Prostaglandin I2, or prostacyclin, is a prostanoid produced predominantly by vascular endothelial cells from arachidonic acid via the cyclooxygenase enzymes and prostacyclin synthase. It is rapidly hydrolyzed in plasma to 6-keto-PGF1α, the stable metabolite commonly measured to estimate PGI2 production.

PGI2 acts mainly through the IP receptor, a Gs-coupled receptor on platelets and vascular smooth muscle. Receptor activation raises intracellular cAMP, causing vasodilation and inhibition of platelet activation and aggregation. In addition, PGI2 can attenuate leukocyte adhesion and may exert anti-proliferative effects on smooth muscle.

Physiologically, PGI2 helps regulate vascular tone and blood flow, opposing the vasoconstrictive and pro-thrombotic actions of thromboxane A2. It contributes to pulmonary vasodilation and overall vascular homeostasis; production is influenced by shear stress, inflammation, and endothelial health.

In clinical contexts, reduced PGI2 signaling can contribute to thrombosis, while pharmacologic prostacyclin analogs are used to treat pulmonary arterial hypertension and other conditions. Epoprostenol, iloprost, treprostinil, and beraprost mimic PGI2, whereas selexipag is an oral IP receptor agonist. The stable metabolite 6-keto-PGF1α is often monitored as a biomarker of PGI2 activity.

NSAIDs reduce PGI2 synthesis by COX inhibition, which can influence thrombotic risk when the balance with thromboxane A2 is altered.