{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:42:19Z","timestamp":1790883739153,"version":"4.1.0"},"reference-count":93,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2018,4,14]],"date-time":"2018-04-14T00:00:00Z","timestamp":1523664000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","award":["FS\/16\/1\/31699"],"award-info":[{"award-number":["FS\/16\/1\/31699"]}],"id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Eicosanoids represent a diverse family of lipid mediators with fundamental roles in physiology and disease. Within the eicosanoid superfamily are prostanoids, which are specifically derived from arachidonic acid by the enzyme cyclooxygenase (COX). COX has two isoforms; COX\u20101 and COX\u20102. COX\u20102 is the therapeutic target for the nonsteroidal anti\u2010inflammatory drug (NSAID) class of pain medications. Of the prostanoids, prostacyclin, first discovered by Sir John Vane in 1976, remains amongst the best studied and retains an impressive pedigree as one of the fundamental cardiovascular protective pathways. Since this time, we have learnt much about how eicosanoids, COX enzymes and prostacyclin function in the cardiovascular system, knowledge that has allowed us, for example, to harness the power of prostacyclin as therapy to treat pulmonary arterial hypertension and peripheral vascular disease. However, there remain many unanswered questions in our basic understanding of the pathways, and how they can be used to improve human health. Perhaps, the most important and controversial outstanding question in the field remains; \u2018how do NSAIDs produce their much publicized cardiovascular side\u2010effects?\u2019 This review summarizes the history, biology and cardiovascular function of key eicosanoids with particular focus on prostacyclin and other COX products and discusses how our knowledge of these pathways can applied in future drug discovery and be used to explain the cardiovascular side\u2010effects of NSAIDs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>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<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.8\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v176.8\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.14167","type":"journal-article","created":{"date-parts":[[2018,2,22]],"date-time":"2018-02-22T02:46:37Z","timestamp":1519267597000},"page":"1038-1050","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":211,"title":["Eicosanoids, prostacyclin and cyclooxygenase in the cardiovascular system"],"prefix":"10.1111","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-546X","authenticated-orcid":false,"given":"Jane A","family":"Mitchell","sequence":"first","affiliation":[{"name":"Cardiothoracic Pharmacology National Heart and Lung Institute London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas S","family":"Kirkby","sequence":"additional","affiliation":[{"name":"Cardiothoracic Pharmacology National Heart and Lung Institute London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,14]]},"reference":[{"key":"e_1_2_8_2_1","first-page":"2121","article-title":"Inherited human cPLA(2alpha) deficiency is associated with impaired eicosanoid biosynthesis, small intestinal ulceration, and platelet dysfunction","volume":"118","author":"Adler DH","year":"2008","journal-title":"J Clin Invest"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.011591"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13877"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13878"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13880"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.108.183160"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.109.193367"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.j1909"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2006.08.079"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061355"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0701100"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200011233432103"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050493"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800033-JLR200"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.70.4.523"},{"key":"e_1_2_8_17_1","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1016\/S0022-3565(24)38195-9","article-title":"Effects of specific inhibition of cyclooxygenase\u20102 on sodium balance, hemodynamics, and vasoactive eicosanoids","volume":"289","author":"Catella\u2010Lawson F","year":"1999","journal-title":"J Pharmacol Exp Ther"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27540"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1155\/2017\/2432958"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60900-9"},{"key":"e_1_2_8_21_1","doi-asserted-by":"crossref","unstructured":"CrescenteM MenkeL ChanMV ArmstrongPC WarnerTD(2019).Eicosanoids in platelets and the effect of their modulation by aspirin in the cardiovascular system (and beyond). 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