{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T02:42:49Z","timestamp":1790908969136,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":669,"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":[[2007,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose:<\/jats:title>\n                    <jats:p>\n                      Aortic complications account for the major mortality in Marfan syndrome (MFS), a connective tissue disorder caused by mutations in\n                      <jats:italic>FBN1<\/jats:italic>\n                      encoding fibrillin\u20101. We hypothesized that MFS impaired endothelial function and nitric oxide (NO) production in the aorta.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach:<\/jats:title>\n                    <jats:p>\n                      Mice (at 3, 6, 9 and 12 months of age) heterozygous for the\n                      <jats:italic>Fbn1<\/jats:italic>\n                      allele encoding a cysteine substitution (\n                      <jats:italic>Fbn1<\/jats:italic>\n                      <jats:sup>C1039G\/+<\/jats:sup>\n                      , Marfan mice, n=75), the most common class of mutation in MFS, were compared with age\u2010matched control littermates (n=75). Thoracic and abdominal aortas from the two groups were studied.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results:<\/jats:title>\n                    <jats:p>\n                      Isometric force measurements revealed that relaxation to ACh (but not to sodium nitroprusside) was diminished in the phenylephrine\u2010precontracted Marfan thoracic aorta at 6 months of age (pEC\n                      <jats:sub>50<\/jats:sub>\n                      =6.12\u00b10.22; maximal response, E\n                      <jats:sub>max<\/jats:sub>\n                      =52.7\u00b16.8%; control: pEC\n                      <jats:sub>50<\/jats:sub>\n                      =7.34\u00b10.19; E\n                      <jats:sub>max<\/jats:sub>\n                      =84.8\u00b12.2%). At one year, both inhibition of NO production with N\n                      <jats:sup>\u03c9<\/jats:sup>\n                      \u2010nitro\u2010\n                      <jats:sc>L<\/jats:sc>\n                      \u2010arginine methyl ester, or denudation of endothelium increased the phenylephrine\u2010stimulated contraction in the control thoracic aorta by 35%, but had no effect in the Marfan aorta, indicating a loss of basal NO production in the Marfan vessel. From 6 months, a reduced phosphorylation of endothelial NOS (eNOS)\n                      <jats:sup>Ser1177<\/jats:sup>\n                      and Akt\n                      <jats:sup>Thr308<\/jats:sup>\n                      detected by Western blotting was observed in the Marfan thoracic aorta, which was accompanied by decreased levels of cGMP. Expressions of Akt and eNOS in the abdominal aorta were not different between the two groups.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications:<\/jats:title>\n                    <jats:p>MFS impairs endothelial function and signaling of NO production in the thoracic aorta, suggesting the importance of NO in the age\u2010related progression of thoracic aortic manifestations.<\/jats:p>\n                    <jats:p>\n                      <jats:italic>British Journal of Pharmacology<\/jats:italic>\n                      (2007)\n                      <jats:bold>150<\/jats:bold>\n                      , 1075\u20131083. doi:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"doi\" xlink:href=\"10.1038\/sj.bjp.0707181\">10.1038\/sj.bjp.0707181<\/jats:ext-link>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/sj.bjp.0707181","type":"journal-article","created":{"date-parts":[[2007,3,5]],"date-time":"2007-03-05T09:03:31Z","timestamp":1173085411000},"page":"1075-1083","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["Endothelial dysfunction and compromised eNOS\/Akt signaling in the thoracic aorta during the progression of Marfan syndrome"],"prefix":"10.1111","volume":"150","author":[{"given":"A W Y","family":"Chung","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K","family":"Au Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S F","family":"Cortes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G G S","family":"Sandor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D P","family":"Judge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H C","family":"Dietz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"van Breemen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2009,1,29]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.1.41"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.17.7.1346"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2005.06.080"},{"key":"e_1_2_8_5_1","first-page":"39","article-title":"Endothelium\u2010dependent vasodilatation in rat aorta is mainly mediated by nitric oxide","volume":"40","author":"Castillo C","year":"1997","journal-title":"Proc West Pharmacol Soc"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(03)00295-X"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcp.1041230304"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.107.3.727"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/21224"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.27.4.849"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2003.08.020"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124287"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1006\/jsre.1995.1126"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(94)90405-7"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000189559.87328.e4"},{"key":"e_1_2_8_17_1","first-page":"1074","article-title":"Aortic aneurysms excluding Marfan's syndrome","volume":"96","author":"Jondeau G","year":"2003","journal-title":"Arch Mal Coeur Vaiss"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420641"},{"key":"e_1_2_8_19_1","first-page":"I\u2010350","article-title":"Fibrillin expression and deposition by vascular endothelial cells: implications for the Marfan syndrome","volume":"94","author":"Kielty CM","year":"1996","journal-title":"Circulation"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.04.032"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-8703(00)90045-0"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1116"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422715"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1997.272.6.C1980"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.54.8.2415"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1159\/000075238"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0264.2004.00410.x"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000049624.99844.3D"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.7.3819"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.8.1.37"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.med.51.1.481"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.92.11.3212"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/306174a0"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0894-7317(03)00407-3"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20041182"},{"key":"e_1_2_8_36_1","first-page":"22","article-title":"A comparative study of the aortic wall in patients with Marfan's syndrome and Erdheim's disease","volume":"10","author":"Sheremet'eva GF","year":"2004","journal-title":"Angiol Sosud Khir"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2006.00232.x"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjhyper.2004.03.678"},{"key":"e_1_2_8_39_1","first-page":"35","article-title":"Possible association of decrease of ATP\u2010induced vascular relaxation with reduction of cyclic GMP during aging","volume":"310","author":"Ueda H","year":"1991","journal-title":"Arch Int Pharmacodyn Ther"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2005.09.089"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.77.1.37"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc0202.101970"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.99.7.909"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/153857440103500118"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.25.6.677"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1042\/bss0710143"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/20.2.153"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.79.4.854"}],"container-title":["British Journal of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0707181","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1038%2Fsj.bjp.0707181","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1038\/sj.bjp.0707181","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T23:43:47Z","timestamp":1697067827000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1038\/sj.bjp.0707181"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,4]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2007,4]]}},"alternative-id":["10.1038\/sj.bjp.0707181"],"URL":"https:\/\/doi.org\/10.1038\/sj.bjp.0707181","archive":["Portico"],"relation":{},"ISSN":["0007-1188","1476-5381"],"issn-type":[{"value":"0007-1188","type":"print"},{"value":"1476-5381","type":"electronic"}],"subject":[],"published":{"date-parts":[[2007,4]]},"assertion":[{"value":"2009-01-29","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}