Prostacyclin synthase (PTGIS) (PTGIS)

Prostacyclin synthase (PTGIS), also known as CYP8A1, is a membrane-bound enzyme in the cytochrome P450 superfamily that catalyzes the isomerization of prostaglandin H2 into prostacyclin (PGI2). Primarily expressed in vascular endothelial cells, PTGIS is the terminal enzyme in the prostacyclin biosynthetic pathway and is essential for maintaining cardiovascular health by producing a molecule that inhibits platelet aggregation and promotes potent vasodilation. Dysregulation of prostacyclin synthesis, often manifested as reduced PTGIS expression or activity, is a central pathological driver in pulmonary arterial hypertension (PAH), atherosclerosis, and preeclampsia. In clinical practice, the pathway is targeted not by direct enzyme modulation but through the administration of exogenous prostacyclin analogs or receptor agonists to compensate for deficient endogenous synthesis. Conversely, common nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the upstream production of the substrates required for prostacyclin synthesis, which can have significant implications for cardiovascular risk and hemostasis.

Other names

Prostaglandin I2 synthasePTGISCYP8A1Cytochrome P450 family 8 subfamily A member 1PGISPGI2 synthaseHydroperoxy icosatetraenoate dehydratase

Drugs modulate this pathway as prostacyclin receptor (IP) agonists, synthetic prostacyclin analogs (mimetics), or upstream inhibitors of cyclooxygenase (COX-1/COX-2) enzymes which deplete the substrate available for prostacyclin synthesis.