{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T10:57:30Z","timestamp":1781953050294,"version":"3.54.5"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":486,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2007,10]]},"abstract":"<jats:sec><jats:title>Background and purpose:<\/jats:title><jats:p>Thoracic aortic dissection is a life\u2010threatening complication of Marfan syndrome, a connective tissue disorder caused by mutations in the gene encoding fibrillin\u20101. We have demonstrated that nitric oxide\u2010mediated endothelial\u2010dependent relaxation is impaired in the thoracic aorta in Marfan syndrome. In the present study, we determined whether the cyclooxygenase (COX)\u2010pathway is involved in the compromised aortic vasomotor function.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental approach:<\/jats:title><jats:p>Thoracic aortae from mice at 3, 6 and 9 months of age, heterozygous for the <jats:italic>Fbn1<\/jats:italic> allele encoding a cysteine substitution (<jats:italic>Fbn1<\/jats:italic>\n<jats:sup>C1039G\/+<\/jats:sup>, \u2018Marfan\u2019, <jats:italic>n<\/jats:italic>=35), were compared with those from age\u2010matched controls (<jats:italic>n<\/jats:italic>=35).<\/jats:p><\/jats:sec><jats:sec><jats:title>Key results:<\/jats:title><jats:p>Isometric force measurement revealed that preincubation with indomethacin, a non\u2010specific COX inhibitor, but not valeryl salicylate, a specific COX\u20101 inhibitor, improved the phenylephrine\u2010induced contractions (at 6 months, EC<jats:sub>50<\/jats:sub> and E<jats:sub>max<\/jats:sub> were increased 4.5\u2010fold and by 45%, respectively) in Marfan aortae. Sensitivity to acetylcholine\u2010induced relaxation was improved 10\u2010fold. Blockade of the thromboxane\u2010endoperoxide receptor by SQ\u201029548 did not affect phenylephrine\u2010mediated contractions in Marfan aortae, although they did respond to the thromboxane analogue, U46619. From 6 months on, phenylephrine\u2010induced secretion of prostacyclin and thromboxane A<jats:sub>2<\/jats:sub> in Marfan aortae was 200% and 40%, respectively, of those in controls. Reduced COX\u20101 expression was detected in Marfan aortae at 3 and 9 months, whilst COX\u20102 expression was increased from 3 months on.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and implications:<\/jats:title><jats:p>The compromised vasomotor function in Marfan thoracic aortae is associated with an imbalanced synthesis of thromboxane A<jats:sub>2<\/jats:sub> and prostacyclin resulting from the differential protein expression of COX\u20101 and COX\u20102.<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2007) <jats:bold>152<\/jats:bold>, 305\u2013312; doi:<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707391\">10.1038\/sj.bjp.0707391<\/jats:ext-link>; published online 16 July 2007<\/jats:p><\/jats:sec>","DOI":"10.1038\/sj.bjp.0707391","type":"journal-article","created":{"date-parts":[[2007,7,20]],"date-time":"2007-07-20T08:19:22Z","timestamp":1184919562000},"page":"305-312","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["Imbalanced synthesis of cyclooxygenase\u2010derived thromboxane A<sub>2<\/sub> and prostacyclin compromises vasomotor function of the thoracic aorta in Marfan syndrome"],"prefix":"10.1111","volume":"152","author":[{"given":"A W Y","family":"Chung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H H C","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"van 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