title: Understanding the role of prostaglandin E2 in regulating human platelet activity in health and disease.
abstract: The platelet thrombus is the major pathologic entity in acute coronary syndromes, and antiplatelet agents are a mainstay of therapy. However, individual patient responsiveness to current antiplatelet drugs is variable, and all drugs carry a risk of bleeding. An understanding of the complex role of Prostaglandin E2 (PGE2) in regulating thrombosis offers opportunities for the development of novel individualized antiplatelet treatment. However, deciphering the platelet regulatory function of PGE2 has long been confounded by non-standardized experimental conditions, extrapolation of murine data to humans, and phenotypic differences in PGE2 response. This review synthesizes past and current knowledge about PGE2 effects on platelet biology, presents a rationale for standardization of experimental protocols, and provides insight into a molecular mechanism by which PGE2-activated pathways could be targeted for new personalized antiplatelet therapy to inhibit pathologic thrombosis without affecting hemostasis.
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN 37232.
authors.forename: Eitan A
authors.initials: EA
authors.lastname: Friedman
authors.affiliation: PO Box 559, Bala Cynwyd, PA 19004; Department of Pharmacology, Vanderbilt University, Nashville, TN 37232.
authors.forename: Martin L
authors.initials: ML
authors.lastname: Ogletree
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN 37232.
authors.forename: Elias V
authors.initials: EV
authors.lastname: Haddad
authors.affiliation: Department of Pharmacology, Vanderbilt University, Nashville, TN 37232. Electronic address: olivier.boutaud@vanderbilt.edu.
authors.forename: Olivier
authors.initials: O
authors.lastname: Boutaud
mesh_terms: D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D019317:Evidence-Based Medicine; D006801:Humans; D051379:Mice; D008955:Models, Cardiovascular; D015539:Platelet Activation; D013045:Species Specificity; D013927:Thrombosis / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015232:Dinoprostone
keywords: Antiplatelet agent; EP3 antagonist; platelet aggregation; platelet inhibitor; platelet reactivity regulation; prostaglandin E(2)