Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond)

Abstract

Platelets are important players in thrombosis and haemostasis with their function being modulated by mediators in the blood and the vascular wall. Among these, eicosanoids can both stimulate and inhibit platelet reactivity. Platelet Cyclooxygenase (COX)-1-generated Thromboxane (TX)A 2 is the primary prostanoid that stimulates platelet aggregation; its action is counter-balanced by prostacyclin, a product of vascular COX. Prostaglandin (PG)D 2 , PGE 2 and 12-hydroxyeicosatraenoic acid (HETE), or 15-HETE, are other prostanoid modulators of platelet activity, but some also play a role in carcinogenesis. Aspirin permanently inhibits platelet COX-1, underlying its anti-thrombotic and anti-cancer action. While the use of aspirin as an anti-cancer drug is increasingly encouraged, its continued use in addition to P 2 Y 12 receptor antagonists for the treatment of cardiovascular diseases is currently debated. Aspirin not only suppresses TXA 2 but also prevents the synthesis of both known and unknown antiplatelet eicosanoid pathways, potentially lessening the efficacy of dual antiplatelet therapies. Linked Articles: This article is part of a themed section on Eicosanoids 35 years from the 1982 Nobel: where are we now? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.8/issuetoc.