{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T12:26:56Z","timestamp":1789648016236,"version":"4.0.0"},"reference-count":34,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Patients with bicuspid aortic valve (BAV) have an increased risk of developing ascending aortic aneurysms. Transforming growth factor-\u03b2 (TGF\u03b2) is a crucial factor of vascular remodeling, the impaired signaling of which can alter the structure and composition of the extracellular matrix. In this study, we analyzed the activity of TGF\u03b2 in aneurysmal and nonaneurysmal ascending aorta from BAV patients, using tricuspid aortic valve (TAV) patients as a reference group.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>The response to exogenous TGF\u03b2 was analyzed with regard to gene expression in primary aortic smooth muscle cells that were isolated from 7 BAV and 5 TAV patients and in valve fibroblasts from 7 BAV and 8 TAV patients. The set of genes that were significantly changed by TGF\u03b2 (217 genes) was compared with gene expression profiles of the ascending aorta from BAV and TAV patients (139 arrays). By principle component analysis, based on the 217 genes, gene expression differed significantly in the intima\/media region between aneurysmal BAV and TAV aortas, driven by the response in TAV patients. During aneurysm development the levels of phosphorylated SMADs and the availability of free TGF\u03b2 were lower in BAV patients compared with TAV. Confocal microscopy analysis showed a higher colocalization of latency associated peptide and latent TGF\u03b2 binding protein 3 in BAV aortas.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>Our findings suggest that TGF\u03b2 activation during aneurysm formation is muted in patients with BAV, possibly as a result of an increased TGF\u03b2 sequestration in the extracellular space.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.114.304996","type":"journal-article","created":{"date-parts":[[2015,3,6]],"date-time":"2015-03-06T03:42:24Z","timestamp":1425613344000},"page":"973-980","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["Aneurysm Development in Patients With a Bicuspid Aortic Valve Is Not Associated With Transforming Growth Factor-\u03b2 Activation"],"prefix":"10.1161","volume":"35","author":[{"given":"Valentina","family":"Paloschi","sequence":"first","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesper R.","family":"G\u00e5din","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaukat","family":"Khan","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna M.","family":"Bj\u00f6rck","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Du","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shohreh","family":"Maleki","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Roy","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan H.M.","family":"Lindeman","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salah A.","family":"Mohamed","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Tsuda","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Franco-Cereceda","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per","family":"Eriksson","sequence":"additional","affiliation":[{"name":"From the Atherosclerosis Research Unit, Department of Medicine, Center for Molecular Medicine (V.P., J.R.G., H.M.B., L.D., S.M., P.E.), Vascular Surgery Section, Department of Molecular Medicine and Surgery (J.R.), and Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery (A.F.-C.), Karolinska Institutet, Stockholm, Sweden; Center for Cardiac Research, Nemours Biomedical Research, Alfred I. duPont Hospital for Children, Wilmington, DE (S.K., T.T.); Department of Vascular Surgery,..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1136\/heart.83.1.81"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.3.2.295"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.300.11.1317"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcts.2011.01.001"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/180297"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2009.12.068"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.113.300675"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/path.2516"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00018"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1177\/1535370213489441"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.112.000034"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/ejcts\/ezs630"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.110.218461"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2011.00286"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1186\/1756-0500-5-636"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.130.1.217"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990301)80:5<756::AID-IJC21>3.0.CO;2-N"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmp018"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1267\/ahc.07002"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1116"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1511"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124287"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000141146.95728.da"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2366"},{"key":"e_1_3_4_27_2","first-page":"42","article-title":"Angiotensin II Receptor Antagonism Reduces Transforming Growth Factor Beta and Smad Signaling in Thoracic Aortic Aneurysm.","volume":"13","author":"Nataatmadja M","year":"2013","unstructured":"Nataatmadja M, West J, Prabowo S, West M. 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