Cardiovascular safety profile of prostaglandin E and prostacyclin analogues: Clinical reports and ex vivo studies on human coronary arteries.

Prostaglandin E1 (PGE1), prostaglandin E2 (PGE2), prostacyclin and their analogues are widely used in clinical practice for their potent biological effects. PGE1/PGE2 analogues, including misoprostol and sulprostone, are primarily used in obstetrics for labour induction, abortion, and postpartum haemorrhage management, whereas PGI2 analogues such as iloprost and treprostinil are key drugs in pulmonary arterial hypertension treatment. Despite structural similarities, these compounds produce contrasting vascular effects due to differences in receptor selectivity, signalling pathways, and tissue distribution. PGE1/PGE2 analogues activate EP receptors, particularly EP1 and EP3 with varying selectivity profile, promoting vasoconstriction and have been associated with cardiovascular complications such as coronary vasospasm. In contrast, PGI2 analogues act mainly on IP receptors, promoting vasodilation, inhibition of platelet aggregation, and beneficial vascular remodelling, with a generally favourable cardiovascular safety profile. Although cardiovascular effects have been reported with both classes of analogues, the underlying mechanisms, and especially their direct effects on human coronary arteries (HCA) remain insufficiently explored. In this context, we combined a review of the clinical and experimental literature that integrates clinical reports with original ex vivo pharmacological investigations on isolated HCA. Both PGE2 and misoprostol induce concentration-dependent vasoconstriction, primarily via EP3 receptors, which is significantly reduced by a TP receptor antagonist, suggesting a potential EP3-TP pathway interaction. All tested PGI2 analogues consistently induced relaxation in our HCA preparations, a finding that aligns with their general improvement of cardiovascular clinical parameters, with only rare exceptions. Together, these findings summarize the cardiovascular effects of clinically-used prostanoids and provide mechanistic insights to optimize their therapeutic use while minimizing cardiovascular risk.