{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T01:20:04Z","timestamp":1792113604152,"version":"4.4.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100004359","name":"Vetenskapsr\u00e5det","doi-asserted-by":"publisher","award":["2020-01442"],"award-info":[{"award-number":["2020-01442"]}],"id":[{"id":"10.13039\/501100004359","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003793","name":"Hj\u00e4rt-Lungfonden","doi-asserted-by":"publisher","award":["20180451"],"award-info":[{"award-number":["20180451"]}],"id":[{"id":"10.13039\/501100003793","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004348","name":"Stockholms L\u00e4ns Landsting","doi-asserted-by":"publisher","award":["20180072"],"award-info":[{"award-number":["20180072"]}],"id":[{"id":"10.13039\/501100004348","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100006285","name":"Magnus Bergvalls Stiftelse","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006285","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007508","name":"Stiftelsen Sigurd and Elsa Goljes Minne","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007508","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Sch\u00f6rling Foundation"},{"name":"Private donation by Mr. Fredrik Lundberg"},{"DOI":"10.13039\/501100004047","name":"Karolinska Institute","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004047","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Mol Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:sec>\n                <jats:title>Abstract<\/jats:title>\n                <jats:p>Bicuspid aortic valve (BAV) is the most common congenital heart malformation frequently associated with ascending aortic aneurysm (AscAA). Epithelial to mesenchymal transition (EMT) may play a role in BAV-associated AscAA. The aim of the study was to investigate the type of EMT associated with BAV aortopathy using patients with a tricuspid aortic valve (TAV) as a reference. The state of the endothelium was further evaluated. Aortic biopsies were taken from patients undergoing open-heart surgery. Aortic intima\/media miRNA and gene expression was analyzed using Affymetrix human transcriptomic array. Histological staining assessed structure, localization, and protein expression. Migration\/proliferation was assessed using ORIS migration assay. We show different EMT types associated with BAV and TAV AscAA. Specifically, in BAV-associated aortopathy, EMT genes related to endocardial cushion formation were enriched. Further, BAV vascular smooth muscle cells were less proliferative and migratory. In contrast, TAV aneurysmal aortas displayed a fibrotic EMT phenotype with medial degenerative insults. Further, non-dilated BAV aortas showed a lower miRNA-200c-associated endothelial basement membrane LAMC1 expression and lower CD31 expression, accompanied by increased endothelial permeability indicated by increased albumin infiltration. Embryonic EMT is a characteristic of BAV aortopathy, associated with endothelial instability and vascular permeability of the non-dilated aortic wall.\n<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Key messages<\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>Embryonic EMT is a feature of BAV-associated aortopathy.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Endothelial integrity is compromised in BAV aortas prior to dilatation.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Non-dilated BAV ascending aortas are more permeable than aortas of tricuspid aortic valve patients.<\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00109-023-02316-5","type":"journal-article","created":{"date-parts":[[2023,5,11]],"date-time":"2023-05-11T06:57:24Z","timestamp":1683788244000},"page":"801-811","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Bicuspid aortic valve aortopathy is characterized by embryonic epithelial to mesenchymal transition and endothelial instability"],"prefix":"10.1007","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9196-7409","authenticated-orcid":false,"given":"David","family":"Freiholtz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Otto","family":"Bergman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karin","family":"L\u00e5ng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flore-Anne","family":"Poujade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valentina","family":"Paloschi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Granath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H. N.","family":"Lindeman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Olsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Franco-Cereceda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Eriksson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna M.","family":"Bj\u00f6rck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"key":"2316_CR1","doi-asserted-by":"publisher","first-page":"561","DOI":"10.1001\/jama.2020.27205","volume":"325","author":"A-S Sillesen","year":"2021","unstructured":"Sillesen A-S, V\u00f8gg O, Pihl C, Raja AA, Sundberg K, Vedel C, Zingenberg H, J\u00f8rgensen FS, Vejlstrup N, Iversen K et al (2021) Prevalence of bicuspid aortic valve and associated aortopathy in Newborns in Copenhagen. Denmark JAMA 325:561\u2013567","journal-title":"Denmark JAMA"},{"key":"2316_CR2","doi-asserted-by":"publisher","first-page":"1650","DOI":"10.1016\/j.jtcvs.2015.12.019","volume":"151","author":"A Masri","year":"2016","unstructured":"Masri A, Kalahasti V, Alkharabsheh S, Svensson LG, Sabik JF, Roselli EE, Hammer D, Johnston DR, Collier P, Rodriguez LL et al (2016) Characteristics and long-term outcomes of contemporary patients with bicuspid aortic valves. J Thorac Cardiovasc Surg 151:1650-1659.e1","journal-title":"J Thorac Cardiovasc Surg"},{"key":"2316_CR3","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2018.1281","volume":"1","author":"MH Guo","year":"2018","unstructured":"Guo MH, Appoo JJ, Saczkowski R, Smith HN, Ouzounian M, Gregory AJ, Herget EJ, Boodhwani M (2018) Association of mortality and acute aortic events with ascending aortic aneurysm: a systematic review and meta-analysis. JAMA Netw Open 1:e181281","journal-title":"JAMA Netw Open"},{"key":"2316_CR4","doi-asserted-by":"crossref","unstructured":"Epstein JA, Franklin H, Epstein Lecture (2010) Cardiac development and implications for heart disease. N Engl J Med 363:1638\u201347","DOI":"10.1056\/NEJMra1003941"},{"key":"2316_CR5","doi-asserted-by":"crossref","unstructured":"Peterson JC, Chughtai M, Wisse LJ, Gittenberger-de Groot AC, Feng Q, Goumans MTH, VanMunsteren JC, Jongbloed MRM, DeRuiter MC (2018) Bicuspid aortic valve formation: Nos3 mutation leads to abnormal lineage patterning of neural crest cells and the second heart field. Dis Model Mech 11","DOI":"10.1242\/dmm.034637"},{"key":"2316_CR6","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3389\/fcvm.2019.00182","volume":"6","author":"S Maleki","year":"2019","unstructured":"Maleki S, Poujade F-A, Bergman O, G\u00e5din JR, Simon N, L\u00e5ng K, Franco-Cereceda A, Body SC, Bj\u00f6rck HM, Eriksson P (2019) Endothelial\/epithelial mesenchymal transition in ascending aortas of patients with bicuspid aortic valve. Front Cardiovasc Med 6:182","journal-title":"Front Cardiovasc Med"},{"key":"2316_CR7","unstructured":"Gehlen J, Stundl A, Debiec R, Fontana F, Krane M, Sharipova D, Nelson CP, Al-Kassou B, Giel AS, Sinning JM et al (2022) Elucidation of the genetic causes of bicuspid aortic valve disease. Cardiovasc Res cvac099"},{"key":"2316_CR8","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1172\/JCI44244","volume":"121","author":"R Jain","year":"2011","unstructured":"Jain R, Engleka KA, Rentschler SL, Manderfield LJ, Li L, Yuan L, Epstein JA (2011) Cardiac neural crest orchestrates remodeling and functional maturation of mouse semilunar valves. J Clin Invest 121:422\u2013430","journal-title":"J Clin Invest"},{"key":"2316_CR9","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1016\/j.devcel.2012.01.014","volume":"22","author":"JL de la Pompa","year":"2012","unstructured":"de la Pompa JL, Epstein JA (2012) Coordinating tissue interactions: notch signaling in cardiac development and disease. Dev Cell 22:244\u2013254","journal-title":"Dev Cell"},{"key":"2316_CR10","doi-asserted-by":"crossref","unstructured":"Gould RA, Aziz H, Woods CE, Seman-Senderos MA, Sparks E, Preuss C, Wunnemann F, Bedja D, Moats CR, McClymont SA et al (2019) ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. Nat Genet 51:42\u201350","DOI":"10.1038\/s41588-018-0265-y"},{"key":"2316_CR11","doi-asserted-by":"crossref","unstructured":"Bjorck HM, Du L, Pulignani S, Paloschi V, Lundstromer K, Kostina AS, Osterholm C, Malashicheva A, Kostareva A, Evangelista A et al (2018) Mechanistic interrogation of bicuspid aortic valve associated aortopathy Leducq C. Altered DNA methylation indicates an oscillatory flow mediated epithelial-to-mesenchymal transition signature in ascending aorta of patients with bicuspid aortic valve. Sci Rep 8:2777","DOI":"10.1038\/s41598-018-20642-4"},{"key":"2316_CR12","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1111\/joim.12833","volume":"285","author":"S Maleki","year":"2019","unstructured":"Maleki S, Cottrill KA, Poujade FA, Bhattachariya A, Bergman O, Gadin JR, Simon N, Lundstromer K, Franco-Cereceda A, Bjorck HM et al (2019) The mir-200 family regulates key pathogenic events in ascending aortas of individuals with bicuspid aortic valves. J Intern Med 285:102\u2013114","journal-title":"J Intern Med"},{"key":"2316_CR13","doi-asserted-by":"crossref","unstructured":"Maleki S, Kjellqvist S, Paloschi V, Magne J, Branca RM, Du L, Hultenby K, Petrini J, Fuxe J, Mibava LC et al (2016) Mesenchymal state of intimal cells may explain higher propensity to ascending aortic aneurysm in bicuspid aortic valves. Sci Rep 6:35712","DOI":"10.1038\/srep35712"},{"key":"2316_CR14","doi-asserted-by":"publisher","first-page":"811","DOI":"10.1161\/ATVBAHA.121.316237","volume":"42","author":"S Jauhiainen","year":"2022","unstructured":"Jauhiainen S, Kiema M, Hedman M, Laakkonen JP (2022) Large Vessel cell heterogeneity and plasticity: focus in aortic aneurysms. Arterioscler Thromb Vasc Biol 42:811\u2013818","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2316_CR15","doi-asserted-by":"publisher","first-page":"1429","DOI":"10.1172\/JCI36183","volume":"119","author":"M Zeisberg","year":"2009","unstructured":"Zeisberg M, Neilson EG (2009) Biomarkers for epithelial-mesenchymal transitions. J Clin Invest 119:1429\u20131437","journal-title":"J Clin Invest"},{"key":"2316_CR16","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.000034","volume":"2","author":"D Wagsater","year":"2013","unstructured":"Wagsater D, Paloschi V, Hanemaaijer R, Hultenby K, Bank RA, Franco-Cereceda A, Lindeman JH, Eriksson P (2013) Impaired collagen biosynthesis and cross-linking in aorta of patients with bicuspid aortic valve. J Am Heart Assoc 2:e000034","journal-title":"J Am Heart Assoc"},{"key":"2316_CR17","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1093\/ejcts\/ezaa440","volume":"59","author":"M Karalko","year":"2021","unstructured":"Karalko M, Stejskal V, Dergel M, Gofus J, Timbilla S, Zaloudkova L, Zacek P, Pojar M, Vojacek J (2021) Histopathological changes in dilated ascending aorta associated with aortic valve cuspidity. Eur J Cardiothorac Surg 59:1103\u20131108","journal-title":"Eur J Cardiothorac Surg"},{"key":"2316_CR18","doi-asserted-by":"publisher","first-page":"1365","DOI":"10.2119\/molmed.2011.00286","volume":"17","author":"L Folkersen","year":"2011","unstructured":"Folkersen L, Wagsater D, Paloschi V, Jackson V, Petrini J, Kurtovic S, Maleki S, Eriksson MJ, Caidahl K, Hamsten A et al (2011) Unraveling divergent gene expression profiles in bicuspid and tricuspid aortic valve patients with thoracic aortic dilatation: the ASAP study. Mol Med 17:1365\u20131373","journal-title":"Mol Med"},{"key":"2316_CR19","first-page":"e118","volume":"40","author":"V Jackson","year":"2011","unstructured":"Jackson V, Petrini J, Caidahl K, Eriksson MJ, Liska J, Eriksson P, Franco-Cereceda A (2011) Bicuspid aortic valve leaflet morphology in relation to aortic root morphology: a study of 300 patients undergoing open-heart surgery. Eur J Cardiothorac Surg 40:e118\u2013e124","journal-title":"Eur J Cardiothorac Surg"},{"key":"2316_CR20","doi-asserted-by":"crossref","unstructured":"Granath C, Freiholtz D, Bredin F, Olsson C, Franco-Cereceda A, Bj\u00f6rck HM (2022) Acetylsalicylic acid is associated with a lower prevalence of ascending aortic aneurysm and a decreased aortic expression of cyclooxygenase 2. J Am Heart Assoc e024346","DOI":"10.1055\/s-0042-1750920"},{"key":"2316_CR21","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.120.017094","volume":"9","author":"LE Bruijn","year":"2020","unstructured":"Bruijn LE, van den Akker BEWM, van Rhijn CM, Hamming JF, Lindeman JHN (2020) Extreme diversity of the human vascular mesenchymal cell landscape. J Am Heart Assoc 9:e017094","journal-title":"J Am Heart Assoc"},{"key":"2316_CR22","first-page":"3107879","volume":"2016","author":"A Malashicheva","year":"2016","unstructured":"Malashicheva A, Kostina D, Kostina A, Irtyuga O, Voronkina I, Smagina L, Ignatieva E, Gavriliuk N, Uspensky V, Moiseeva O et al (2016) Phenotypic and functional changes of endothelial and smooth muscle cells in thoracic aortic aneurysms. Int J Vasc Med 2016:3107879","journal-title":"Int J Vasc Med"},{"key":"2316_CR23","doi-asserted-by":"crossref","unstructured":"Wu T, Hu E, Xu S, Chen M, Guo P, Dai Z, Feng T, Zhou L, Tang W, Zhan L et al (2021) clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation (Camb) 2:100141","DOI":"10.1016\/j.xinn.2021.100141"},{"key":"2316_CR24","doi-asserted-by":"crossref","unstructured":"Moushi A, Pillar N, Keravnou A, Soteriou M, Shomron N, Cariolou MA, Bashiardes E (2020) MicroRNAs in ascending thoracic aortic aneurysms. Biosci Rep 40:BSR20200218","DOI":"10.1042\/BSR20200218"},{"key":"2316_CR25","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1097\/MOH.0000000000000239","volume":"23","author":"P Lertkiatmongkol","year":"2016","unstructured":"Lertkiatmongkol P, Liao D, Mei H, Hu Y, Newman PJ (2016) Endothelial functions of PECAM-1 (CD31). Curr Opin Hematol 23:253\u2013259","journal-title":"Curr Opin Hematol"},{"key":"2316_CR26","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1007\/s00246-009-9611-2","volume":"31","author":"S Rentschler","year":"2010","unstructured":"Rentschler S, Jain R, Epstein JA (2010) Tissue-tissue interactions during morphogenesis of the outflow tract. Pediatr Cardiol 31:408\u2013413","journal-title":"Pediatr Cardiol"},{"key":"2316_CR27","first-page":"1986","volume":"119","author":"FA High","year":"2009","unstructured":"High FA, Jain R, Stoller JZ, Antonucci NB, Lu MM, Loomes KM, Kaestner KH, Pear WS, Epstein JA (2009) Murine Jagged1\/notch signaling in the second heart field orchestrates Fgf8 expression and tissue-tissue interactions during outflow tract development. J Clin Invest 119:1986\u20131996","journal-title":"J Clin Invest"},{"key":"2316_CR28","doi-asserted-by":"publisher","first-page":"27067","DOI":"10.1074\/jbc.M115.684753","volume":"290","author":"SL Lewandowski","year":"2015","unstructured":"Lewandowski SL, Janardhan HP, Trivedi CM (2015) Histone deacetylase 3 Coordinates deacetylase-independent epigenetic silencing of transforming growth factor-beta1 (TGF-beta1) to orchestrate second heart field development. J Biol Chem 290:27067\u201327089","journal-title":"J Biol Chem"},{"key":"2316_CR29","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1093\/cvr\/cvt132","volume":"99","author":"HM Phillips","year":"2013","unstructured":"Phillips HM, Mahendran P, Singh E, Anderson RH, Chaudhry B, Henderson DJ (2013) Neural crest cells are required for correct positioning of the developing outflow cushions and pattern the arterial valve leaflets. Cardiovasc Res 99:452\u2013460","journal-title":"Cardiovasc Res"},{"key":"2316_CR30","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1093\/cvr\/cvv175","volume":"108","author":"JR Moonen","year":"2015","unstructured":"Moonen JR, Lee ES, Schmidt M, Maleszewska M, Koerts JA, Brouwer LA, van Kooten TG, van Luyn MJ, Zeebregts CJ, Krenning G et al (2015) Endothelial-to-mesenchymal transition contributes to fibro-proliferative vascular disease and is modulated by fluid shear stress. Cardiovasc Res 108:377\u2013386","journal-title":"Cardiovasc Res"},{"key":"2316_CR31","doi-asserted-by":"publisher","first-page":"2326","DOI":"10.1002\/bit.25291","volume":"111","author":"GJ Mahler","year":"2014","unstructured":"Mahler GJ, Frendl CM, Cao Q, Butcher JT (2014) Effects of shear stress pattern and magnitude on mesenchymal transformation and invasion of aortic valve endothelial cells. Biotechnol Bioeng 111:2326\u20132337","journal-title":"Biotechnol Bioeng"},{"key":"2316_CR32","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.matbio.2016.06.008","volume":"57\u201358","author":"J Di Russo","year":"2017","unstructured":"Di Russo J, Hannocks M-J, Luik A-L, Song J, Zhang X, Yousif L, Aspite G, Hallmann R, Sorokin L (2017) Vascular laminins in physiology and pathology. Matrix Biol 57\u201358:140\u2013148","journal-title":"Matrix Biol"},{"key":"2316_CR33","doi-asserted-by":"publisher","first-page":"101","DOI":"10.4161\/cam.22680","volume":"7","author":"LF Yousif","year":"2013","unstructured":"Yousif LF, Di Russo J, Sorokin L (2013) Laminin isoforms in endothelial and perivascular basement membranes. Cell Adh Migr 7:101\u2013110","journal-title":"Cell Adh Migr"},{"key":"2316_CR34","doi-asserted-by":"publisher","first-page":"29701","DOI":"10.1074\/jbc.M611452200","volume":"282","author":"H Fujiwara","year":"2007","unstructured":"Fujiwara H, Hayashi Y, Sanzen N, Kobayashi R, Weber CN, Emoto T, Futaki S, Niwa H, Murray P, Edgar D, Sekiguchi K (2007) Regulation of mesodermal differentiation of mouse embryonic stem cells by basement membranes. J Biol Chem 282:29701\u201329711","journal-title":"J Biol Chem"},{"key":"2316_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109268","volume":"35","author":"M Richards","year":"2021","unstructured":"Richards M, Pal S, Sj\u00f6berg E, Martinsson P, Venkatraman L, Claesson-Welsh L (2021) Intra-vessel heterogeneity establishes enhanced sites of macromolecular leakage downstream of laminin \u03b15. Cell Rep 35:109268","journal-title":"Cell Rep"},{"key":"2316_CR36","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202001936RRR","volume":"35","author":"M Khajavi","year":"2021","unstructured":"Khajavi M, Zhou Y, Schiffer AJ, Bazinet L, Birsner AE, Zon L, D\u2019Amato RJ (2021) Identification of Basp1 as a novel angiogenesis-regulating gene by multi-model system studies. FASEB J 35:e21404","journal-title":"FASEB J"},{"key":"2316_CR37","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1002\/dvdy.20648","volume":"235","author":"M Sakabe","year":"2006","unstructured":"Sakabe M, Ikeda K, Nakatani K, Kawada N, Imanaka-Yoshida K, Yoshida T, Yamagishi T, Nakajima Y (2006) Rho kinases regulate endothelial invasion and migration during valvuloseptal endocardial cushion tissue formation. Dev Dyn 235:94\u2013104","journal-title":"Dev Dyn"},{"key":"2316_CR38","doi-asserted-by":"crossref","unstructured":"Grewal N, Gittenberger-de Groot AC, von der Thusen J, Wisse LJ, Bartelings MM, DeRuiter MC, Poelmann RE (2020) The development of the ascending aortic wall in tricuspid and bicuspid aortic valve: a process from maturation to degeneration.\u00a0J Clin Med\u00a09(4):908.\u00a0Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/32225051\/","DOI":"10.3390\/jcm9040908"}],"container-title":["Journal of Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-023-02316-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00109-023-02316-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00109-023-02316-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T06:04:02Z","timestamp":1687845842000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00109-023-02316-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,10]]},"references-count":38,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2023,7]]}},"alternative-id":["2316"],"URL":"https:\/\/doi.org\/10.1007\/s00109-023-02316-5","relation":{},"ISSN":["0946-2716","1432-1440"],"issn-type":[{"value":"0946-2716","type":"print"},{"value":"1432-1440","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,10]]},"assertion":[{"value":"15 December 2022","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 February 2023","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 April 2023","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2023","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The study was approved by the Human Research Ethics Committee in Stockholm (application nos. 2006\/784\u201331\/1 and 2012\/1633\u201331\/4), and written consent was obtained from all patients according to the declaration of Helsinki.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The authors declare that they have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}