Prostaglandin-endoperoxide synthase (PGHS) (PGHS)

Prostaglandin-endoperoxide synthase (PGHS), also known as cyclooxygenase (COX), is a bifunctional enzyme that catalyzes the conversion of arachidonic acid to prostaglandin H2 (PGH2) [1, 2]. This reaction is the committed and rate-limiting step in the biosynthesis of prostanoids, including prostaglandins, thromboxanes, and prostacyclin [3]. In endothelial cells, PGHS activity is primarily responsible for the production of prostacyclin (PGI2), a critical signaling molecule that promotes vasodilation and inhibits platelet aggregation [4]. The enzyme exists in two main isoforms: PGHS-1 (COX-1), which is constitutively expressed in most tissues, and PGHS-2 (COX-2), which is typically induced during inflammation but also maintains constitutive expression in the vascular endothelium [1, 2]. Endothelial PGHS is a major therapeutic target for nonsteroidal anti-inflammatory drugs (NSAIDs) and antithrombotic agents like aspirin [3, 5]. Aspirin's cardioprotective effect relies on the differential recovery of PGHS activity; while platelets cannot resynthesize the enzyme after irreversible inhibition, nucleated endothelial cells can restore PGI2 production [4, 5]. Conversely, selective COX-2 inhibitors can suppress endothelial PGI2 without affecting platelet thromboxane, which may lead to an increased risk of thrombotic cardiovascular events [4, 6]. Understanding the balance of PGHS activity across different cell types is essential for evaluating the safety and efficacy of anti-inflammatory therapies [3].

Other names

CyclooxygenaseCOXPTGSProstaglandin G/H synthaseProstaglandin synthaseEndothelial PGHSCOX-1COX-2

Inhibition of the cyclooxygenase (COX) active site of the enzyme, preventing the conversion of arachidonic acid into prostaglandin G2 (PGG2) and subsequently prostaglandin H2 (PGH2), thereby reducing the synthesis of downstream prostanoids like prostacyclin and thromboxane.