Cyclooxygenase-derived vasodilatory prostanoid pathway (COX-PGI2 pathway)

The cyclooxygenase-derived vasodilatory prostanoid pathway in the endothelium is a fundamental regulatory system for cardiovascular health. It primarily involves the production of prostacyclin (PGI2) from arachidonic acid through the sequential actions of cyclooxygenase (COX) enzymes and prostacyclin synthase (PTGIS) (Moncada & Vane, 1979; Majed & Khalil, 2012). Once synthesized, PGI2 acts on the prostacyclin (IP) receptor located on vascular smooth muscle cells and platelets, stimulating adenylyl cyclase to increase intracellular cAMP (Giles et al., 2012). This increase in cAMP promotes potent vasodilation and prevents thrombus formation by inhibiting platelet aggregation. This pathway plays a protective role against atherosclerosis and hypertension, and its impairment is a key driver in the pathogenesis of pulmonary arterial hypertension (PAH) (Galie et al., 2016). Pharmacological modulation includes the use of PGI2 analogs like epoprostenol and IP receptor agonists like selexipag to treat PAH (Sitbon & Vonk Noordegraaf, 2017). Conversely, non-steroidal anti-inflammatory drugs (NSAIDs) inhibit the COX enzymes within this pathway, which can lead to reduced PGI2 levels and an increased risk of cardiovascular events (Grosser et al., 2006).

Other names

Prostacyclin pathwayEndothelial PGI2 pathwayCOX-PTGIS-IP axisProstanoid vasodilatory pathway

The pathway is modulated by IP receptor agonists that increase intracellular cAMP to promote vasodilation, and by COX inhibitors that reduce the synthesis of PGH2, the precursor to all prostanoids.