{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:37:07Z","timestamp":1790516227450,"version":"4.1.0"},"reference-count":43,"publisher":"Wiley","issue":"22","license":[{"start":{"date-parts":[[2017,8,11]],"date-time":"2017-08-11T00:00:00Z","timestamp":1502409600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004410","name":"T\u00fcrkiye Bilimsel ve Teknolojik Ara\u015ftirma Kurumu","doi-asserted-by":"publisher","award":["BIDEB\u20102214"],"award-info":[{"award-number":["BIDEB\u20102214"]}],"id":[{"id":"10.13039\/501100004410","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001677","name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001677","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":[[2017,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>The side effects of cyclooxygenase\u20102 (COX\u20102) inhibitors on the cardiovascular system could be associated with reduced prostaglandin (PG)I<jats:sub>2<\/jats:sub> synthesis. Microsomal PGE synthase\u20101 (mPGES\u20101) catalyses the formation of PGE<jats:sub>2<\/jats:sub> from COX\u2010derived PGH<jats:sub>2<\/jats:sub>. This enzyme is induced under inflammatory conditions and constitutes an attractive target for novel anti\u2010inflammatory drugs. However, it is not known whether mPGES\u20101 inhibitors could be devoid of cardiovascular side effects. The aim of this study was to compare, <jats:italic>in vitro,<\/jats:italic> the effects of mPGES\u20101 and COX\u20102 inhibitors on vascular tone in human blood vessels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p>The vascular tone and prostanoid release from internal mammary artery (IMA) and saphenous vein (SV) incubated for 30\u00a0min with inhibitors of mPGES\u20101 or COX\u20102 were investigated under normal and inflammatory conditions.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>In inflammatory conditions, mPGES\u20101 and COX\u20102 proteins were more expressed, and increased levels of PGE<jats:sub>2<\/jats:sub> and PGI<jats:sub>2<\/jats:sub> were released. COX\u20102 and NOS inhibitors increased noradrenaline induced vascular contractions in IMA under inflammatory conditions while no effect was observed in SV. Interestingly, the mPGES\u20101 inhibitor significantly reduced (30\u201340%) noradrenaline\u2010induced contractions in both vessels. This effect was reversed by an IP (PGI<jats:sub>2<\/jats:sub> receptor) antagonist but not modified by NOS inhibition. Moreover, PGI<jats:sub>2<\/jats:sub> release was increased with the mPGES\u20101 inhibitor and decreased with the COX\u20102 inhibitor, while both inhibitors reduced PGE<jats:sub>2<\/jats:sub> release.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p>In contrast to COX\u20102 inhibition, inhibition of mPGES\u20101 reduced vasoconstriction by increasing PGI<jats:sub>2<\/jats:sub> synthesis. Targeting mPGES\u20101 could provide a lower risk of cardiovascular side effects, compared with those of the COX\u20102 inhibitors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Linked Articles<\/jats:title><jats:p>This article is part of a themed section on Targeting Inflammation to Reduce Cardiovascular Disease Risk. 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.v174.22\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bph.v174.22\/issuetoc<\/jats:ext-link> and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcp.v82.4\/issuetoc\">http:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/bcp.v82.4\/issuetoc<\/jats:ext-link><\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13939","type":"journal-article","created":{"date-parts":[[2017,7,4]],"date-time":"2017-07-04T13:17:57Z","timestamp":1499174277000},"page":"4087-4098","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["<b>I<\/b>nhibition of microsomal PGE synthase\u20101 reduces human vascular tone by increasing PGI<sub>2<\/sub>: a safer alternative to COX\u20102 inhibition"],"prefix":"10.1111","volume":"174","author":[{"given":"Gulsev","family":"Ozen","sequence":"first","affiliation":[{"name":"INSERM U1148  Paris France"},{"name":"Faculty of Pharmacy, Department of Pharmacology Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Gomez","sequence":"additional","affiliation":[{"name":"INSERM U1148  Paris France"},{"name":"Department of Infection, Immunity and Cardiovascular Disease, School of Medicine and Biomedical Sciences University of Sheffield  Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Armond","family":"Daci","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Deschildre","sequence":"additional","affiliation":[{"name":"INSERM U1148  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia","family":"Boubaya","sequence":"additional","affiliation":[{"name":"INSERM U1148  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Onder","family":"Teskin","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular Surgery Aile Hospital  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"B Sonmez","family":"Uyde\u015f\u2010Do\u011fan","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per\u2010Johan","family":"Jakobsson","sequence":"additional","affiliation":[{"name":"Unit of Rheumatology, Department of Medicine Solna, Karolinska Institute and Unit of Rheumatology Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Longrois","sequence":"additional","affiliation":[{"name":"INSERM U1148  Paris France"},{"name":"AP\u2010HP CHU X. Bichat, Department of Anesthesia and Intensive Care University Paris Diderot, Sorbonne Paris\u2010Cit\u00e9, UMR\u2010S1148  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gokce","family":"Topal","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, Department of Pharmacology Istanbul University  Istanbul Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0734-3359","authenticated-orcid":false,"given":"Xavier","family":"Norel","sequence":"additional","affiliation":[{"name":"INSERM U1148  Paris France"},{"name":"University Paris Diderot, Sorbonne Paris\u2010Cit\u00e9, UMR\u2010S1148  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,11]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.011591"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13348"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13353"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13354"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.joca.2008.04.022"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)60900-9"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.18.10.1655"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2007.02555.x"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.115.228932"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.112.119479"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI27540"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.12856"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn1137"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn287"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01264.x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2004.08.064"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.plefa.2013.04.004"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20061617"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-011209-153129"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9150(97)00114-7"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.2003.01848.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.13.7220"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.260"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.06.022"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2013.09.001"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.011008.145638"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2010.01.003"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1001388"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200012)43:12<2687::AID-ANR8>3.0.CO;2-9"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1100\/tsw.2007.184"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0214752"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/annrheumdis-2016-209124.27"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20160463"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.prostaglandins.2015.04.008"},{"issue":"19","key":"e_1_2_10_36_1","first-page":"322","article-title":"Enhanced nitric oxide\u2010mediated vascular relaxation in radial artery compared with internal mammary artery or saphenous vein","volume":"100","author":"Shapira OM","year":"1999","journal-title":"Circulation"},{"key":"e_1_2_10_37_1","first-page":"422","article-title":"Mechanism underlying enhanced endothelium\u2010dependent vasodilatation in thoracic aorta of early stage streptozotocin\u2010induced diabetic mice","volume":"24","author":"Shen B","year":"2013","journal-title":"Acta Pharmacol Sin"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv1037"},{"key":"e_1_2_10_39_1","first-page":"1122","article-title":"Inducible L\u2010arginine\/nitric oxide pathway in human internal mammary artery and saphenous vein","volume":"268","author":"Thorin\u2010Trescases N","year":"1995","journal-title":"Am J Physiol"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2011.04.002"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0606586103"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.973685"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.108.138776"},{"key":"e_1_2_10_44_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003787"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fbph.13939","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/bph.13939","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,29]],"date-time":"2023-09-29T12:28:25Z","timestamp":1695990505000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/bph.13939"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,11]]},"references-count":43,"journal-issue":{"issue":"22","published-print":{"date-parts":[[2017,11]]}},"alternative-id":["10.1111\/bph.13939"],"URL":"https:\/\/doi.org\/10.1111\/bph.13939","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,11]]},"assertion":[{"value":"2016-11-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-06-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-08-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}