{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T20:32:11Z","timestamp":1793046731011,"version":"4.5.0"},"reference-count":28,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2013,1,23]]},"abstract":"\n Background<\/jats:title>\n \n Patients with bicuspid aortic valve (\n BAV<\/jats:styled-content>\n ) have an increased risk of developing ascending aortic aneurysm. In the present study, collagen homeostasis in nondilated and dilated aorta segments from patients with\n BAV<\/jats:styled-content>\n was studied, with normal and dilated aortas from tricuspid aortic valve (\n TAV<\/jats:styled-content>\n ) patients as reference.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Ascending aortas from 56 patients were used for biochemical and morphological analyses of collagen.\n mRNA<\/jats:styled-content>\n expression was analyzed in 109 patients. Collagen turnover rates were similar in nondilated and dilated aortas of\n BAV<\/jats:styled-content>\n patients, showing that aneurysmal formation in\n BAV<\/jats:styled-content>\n is, in contrast to\n TAV<\/jats:styled-content>\n ,\n not<\/jats:italic>\n associated with an increased collagen turnover. However,\n BAV<\/jats:styled-content>\n in general was associated with an increased aortic collagen turnover compared with nondilated aortas of\n TAV<\/jats:styled-content>\n patients. Importantly, the ratio of hydroxylysyl pyridinoline (HP) to lysyl pyridinoline (LP), 2 distinct forms of collagen cross\u2010linking, was lower in dilated aortas from patients with\n BAV<\/jats:styled-content>\n , which suggests that\n BAV<\/jats:styled-content>\n is associated with a defect in the posttranslational collagen modification. This suggests a deficiency at the level of lysyl hydroxylase (\n \n PLOD<\/jats:styled-content>\n 1\n <\/jats:italic>\n ), which was confirmed by\n mRNA<\/jats:styled-content>\n and protein analyses that showed reduced\n \n PLOD<\/jats:styled-content>\n 1\n <\/jats:italic>\n expression but normal\n lysyl oxidase<\/jats:italic>\n expression in dilated aortas from patients with\n BAV<\/jats:styled-content>\n . This suggests that impaired collagen cross\u2010linking in\n BAV<\/jats:styled-content>\n patients may be attributed to changes in the expression and\/or activity of\n \n PLOD<\/jats:styled-content>\n 1\n <\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our results demonstrate an impaired biosynthesis and posttranslational modification of collagen in aortas of patients with\n BAV<\/jats:styled-content>\n , which may explain the increased aortic aneurysm formation in\n BAV<\/jats:styled-content>\n patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.112.000034","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T16:49:11Z","timestamp":1369414151000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":60,"title":["Impaired Collagen Biosynthesis and Cross\u2010linking in Aorta of Patients With Bicuspid Aortic Valve"],"prefix":"10.1161","volume":"2","author":[{"given":"Dick","family":"W\u00e5gs\u00e4ter","sequence":"first","affiliation":[{"name":"Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska University hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Paloschi","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska University hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roeland","family":"Hanemaaijer","sequence":"additional","affiliation":[{"name":"TNO Metabolic Health Research, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kjell","family":"Hultenby","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruud A.","family":"Bank","sequence":"additional","affiliation":[{"name":"Department of Medical Biology, University Medical Center Groningen, Groningen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Franco\u2010Cereceda","sequence":"additional","affiliation":[{"name":"Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H. N.","family":"Lindeman","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery, Leiden University Medical Center, Leiden, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Eriksson","sequence":"additional","affiliation":[{"name":"Atherosclerosis Research Unit, Center for Molecular Medicine, Department of Medicine, Karolinska University hospital, Karolinska Institutet, Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.3.2.295"},{"issue":"1","key":"e_1_3_3_3_2","first-page":"II291","article-title":"Failure to prevent progressive dilation of ascending aorta by aortic valve replacement in patients with bicuspid aortic valve: comparison with tricuspid aortic valve","volume":"108","author":"Yasuda H","year":"2003","unstructured":"Yasuda H, Nakatani S, Stugaard M, Tsujita\u2010Kuroda Y, Bando K, Kobayashi J, Yamagishi M, Kitakaze M, Kitamura S, Miyatake K. Failure to prevent progressive dilation of ascending aorta by aortic valve replacement in patients with bicuspid aortic valve: comparison with tricuspid aortic valve. Circulation. 2003; 108(suppl 1):II291\u2013II294.","journal-title":"Circulation"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.82.1.19"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000055441.28842.0A"},{"key":"e_1_3_3_6_2","first-page":"369","article-title":"Bicuspid aortic valve: abnormal aortic elastic properties","volume":"11","author":"Nistri S","year":"2002","unstructured":"Nistri S, Sorbo MD, Basso C, Thiene G. Bicuspid aortic valve: abnormal aortic elastic properties. J Heart Valve Dis. 2002;11:369\u2013373; discussion 373\u2010364.","journal-title":"J Heart Valve Dis"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2006.09.118"},{"key":"e_1_3_3_8_2","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1177\/096721099400200412","article-title":"Failure of elastin or collagen as possible critical connective tissue alterations underlying aneurysmal dilatation","volume":"2","author":"Dobrin PB","year":"1994","unstructured":"Dobrin PB, Mrkvicka R. Failure of elastin or collagen as possible critical connective tissue alterations underlying aneurysmal dilatation. Cardiovasc Surg. 1994;2:484\u2013488.","journal-title":"Cardiovasc Surg"},{"key":"e_1_3_3_9_2","first-page":"e118","article-title":"Bicuspid aortic valve leaflet morphology in relation to aortic root morphology: a study of 300 patients undergoing open\u2010heart surgery","volume":"40","author":"Jackson V","year":"2011","unstructured":"Jackson V, Petrini J, Caidahl K, Eriksson MJ, Liska J, Eriksson P, Franco\u2010Cereceda A. Bicuspid aortic valve leaflet morphology in relation to aortic root morphology: a study of 300 patients undergoing open\u2010heart surgery. Eur J Cardiothorac Surg. 2011;40:e118\u2013e124.","journal-title":"Eur J Cardiothorac Surg"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2011.08.043"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2008.02.001"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0910312107"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01002772"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2009.080561"},{"key":"e_1_3_3_15_2","first-page":"171","article-title":"A histochemical and electron microscopic study on the collagen of nerves in the domestic fowl","volume":"137","author":"Luque EH","year":"1983","unstructured":"Luque EH, Angulo E, Montes GS. A histochemical and electron microscopic study on the collagen of nerves in the domestic fowl. J Anat. 1983;137:171\u2013176.","journal-title":"J Anat"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00266843"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00286"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0b013e3283477797"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2011.392"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1177\/0363546507311092"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1096-7192(02)00036-7"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2005.04.002"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2516"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2008.01.001"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1067\/msg.2002.121421"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2005.04.014"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M608830200"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2012.06.043"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1010-7940(02)00833-3"}],"container-title":["Journal of the American Heart Association"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/JAHA.112.000034","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,6]],"date-time":"2025-02-06T08:34:07Z","timestamp":1738830847000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/JAHA.112.000034"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,1,23]]},"references-count":28,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1,23]]}},"alternative-id":["10.1161\/JAHA.112.000034"],"URL":"https:\/\/doi.org\/10.1161\/jaha.112.000034","relation":{},"ISSN":["2047-9980"],"issn-type":[{"value":"2047-9980","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,1,23]]},"assertion":[{"value":"2012-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-01-17","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-02-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e000034"}}