{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T09:44:23Z","timestamp":1790934263178,"version":"4.1.0"},"reference-count":51,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2006,12,1]],"date-time":"2006-12-01T00:00:00Z","timestamp":1164931200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2006,12]]},"abstract":"<jats:p>\n                    Recent data have suggested that regular consumption of nonsteroid anti\u2010inflammatory drugs (NSAIDs), particularly selective inhibitors of cyclo\u2010oxygenase\u20102 (COX\u20102), is associated with an increased risk of thrombotic events. It has been suggested that this is due to NSAIDs reducing the release from the endothelium of the antithrombotic mediator prosta\u2010glandin I2 as a result of inhibition of endothelial COX\u20102. Here, however, we show that despite normal human vessels and endothelial cells containing cyclo\u2010oxygenase\u20101 (COX\u20101) without any detectable COX\u20102, COX\u20101 in vessels or endothelial cells is more readily inhibited by NSAIDs and COX\u20102\u2010selective drugs than COX\u20101 in platelets (\n                    <jats:italic>e.g.<\/jats:italic>\n                    , log IC\n                    <jats:sub>50<\/jats:sub>\n                    \u00b1SEM values for endothelial cells\n                    <jats:italic>vs.<\/jats:italic>\n                    platelets: naproxen \u22125.59\u00b10.07\n                    <jats:italic>vs.<\/jats:italic>\n                    \u22124.81\u00b10.04; rofecoxib\u20134.93\u00b10.04\n                    <jats:italic>vs.<\/jats:italic>\n                    \u22123.75\u00b10.03;\n                    <jats:italic>n<\/jats:italic>\n                    =7). In broken cell preparations, the selectivities of the tested drugs toward endothelial cell over platelet COX\u20101 were lost. These observations suggest that variations in cellular conditions, such as endogenous peroxide tone and substrate supply, and not the isoform of cyclo\u2010oxygenase present, dictate the effects of NSAIDs on endothelial cells\n                    <jats:italic>vs.<\/jats:italic>\n                    platelets. This may well be because the platelet is not a good representative of COX\u20101 activity within the body as it produces prostanoids in an explosive burst that does not reflect tonic release from other cells. The results reported here can offer an explanation for the apparent ability of NSAIDs and COX\u20102\u2010selective inhibitors to increase the risk of myocardial infarction and stroke.\u2014Mitchell, J. A., Lucas, R., Vojnovic, I., Hasan, K., Pepper, J. R., Warner, T. D. Stronger inhibition by nonsteroid anti\u2010inflammatory drugs of cyclooxygenase\u20101 in endothelial cells than platelets offers an explanation for increased risk of thrombotic events. FASEB J. 20, 2468\u20132475 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.06-6615com","type":"journal-article","created":{"date-parts":[[2006,12,1]],"date-time":"2006-12-01T18:52:49Z","timestamp":1164999169000},"page":"2468-2475","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":69,"title":["Stronger inhibition by nonsteroid anti\u2010inflammatory drugs of cyclooxygenase\u20101 in endothelial cells than platelets offers an explanation for increased risk of thrombotic events"],"prefix":"10.1096","volume":"20","author":[{"given":"Jane A.","family":"Mitchell","sequence":"first","affiliation":[{"name":"Cardiothoracic Pharmacology, Unit of Critical Care Medicine Royal Brompton Hospital, Imperial College School of Medicine London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Lucas","sequence":"additional","affiliation":[{"name":"Cardiothoracic Pharmacology, Unit of Critical Care Medicine Royal Brompton Hospital, Imperial College School of Medicine London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivana","family":"Vojnovic","sequence":"additional","affiliation":[{"name":"The William Harvey Research Institute Barts and the London, Queen Mary's School of Medicine and Dentistry London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamrul","family":"Hasan","sequence":"additional","affiliation":[{"name":"Cardiothoracic Pharmacology, Unit of Critical Care Medicine Royal Brompton Hospital, Imperial College School of Medicine London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Pepper","sequence":"additional","affiliation":[{"name":"Cardiothoracic Pharmacology, Unit of Critical Care Medicine Royal Brompton Hospital, Imperial College School of Medicine London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy D.","family":"Warner","sequence":"additional","affiliation":[{"name":"The William Harvey Research Institute Barts and the London, Queen Mary's School of Medicine and Dentistry London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1155\/1996\/850710"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2036.2004.02037.x"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27291"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1929"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.03-0645rev"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/hh2001.098351"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2005.10.001"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI110814"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.159.11.1248"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/heart.85.3.265"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.1.272"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3565(24)38195-9"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27540"},{"key":"e_1_2_6_15_1","first-page":"1092","article-title":"Adenomatous Polyp Prevention on Vioxx (APPROVe) Trial Investigators","volume":"352","author":"Bresalier R. 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