{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:27:11Z","timestamp":1791296831587,"version":"4.1.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2009,8,11]]},"abstract":"<jats:p>\n            <jats:bold>\n              <jats:italic>Background\u2014<\/jats:italic>\n            <\/jats:bold>\n            Marfan syndrome (MFS) is caused by mutations in the fibrillin-1 gene and dysregulation of transforming growth factor-\u03b2 (TGF-\u03b2). Recent evidence suggests that losartan, an angiotensin II type 1 blocker that blunts TGF-\u03b2 activation, may be an effective treatment for MFS. We hypothesized that dysregulation of TGF-\u03b2 might be mirrored in circulating TGF-\u03b2 concentrations.\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Methods and Results\u2014<\/jats:italic>\n            <\/jats:bold>\n            Serum obtained from MFS mutant mice (\n            <jats:italic>Fbn1<\/jats:italic>\n            <jats:sup>\n              <jats:italic>C1039G<\/jats:italic>\n              \/+\n            <\/jats:sup>\n            ) treated with losartan was analyzed for circulating TGF-\u03b21 concentrations and compared with those from placebo-treated and wild-type mice. Aortic root size was measured by echocardiography. Data were validated in patients with MFS and healthy individuals. In mice, circulating total TGF-\u03b21 concentrations increased with age and were elevated in older untreated\n            <jats:italic>Fbn1<\/jats:italic>\n            <jats:sup>\n              <jats:italic>C1039G<\/jats:italic>\n              \/+\n            <\/jats:sup>\n            mice compared with wild-type mice (\n            <jats:italic>P<\/jats:italic>\n            =0.01; n=16; mean\u00b1SEM, 115\u00b18 ng\/mL versus n=17; mean\u00b1SEM, 92\u00b14 ng\/mL). Losartan-treated\n            <jats:italic>Fbn1<\/jats:italic>\n            <jats:sup>\n              <jats:italic>C1039G<\/jats:italic>\n              \/+\n            <\/jats:sup>\n            mice had lower total TGF-\u03b21 concentrations compared with age-matched\n            <jats:italic>Fbn1<\/jats:italic>\n            <jats:sup>\n              <jats:italic>C1039G<\/jats:italic>\n              \/+\n            <\/jats:sup>\n            mice treated with placebo (\n            <jats:italic>P<\/jats:italic>\n            =0.01; n=18; 90\u00b15 ng\/mL), and circulating total TGF-\u03b21 levels were indistinguishable from those of age-matched wild-type mice (\n            <jats:italic>P<\/jats:italic>\n            =0.8). Correlation was observed between circulating TGF-\u03b21 levels and aortic root diameters in\n            <jats:italic>Fbn1<\/jats:italic>\n            <jats:sup>\n              <jats:italic>C1039G<\/jats:italic>\n              \/+\n            <\/jats:sup>\n            and wild-type mice (\n            <jats:italic>P<\/jats:italic>\n            =0.002). In humans, circulating total TGF-\u03b21 concentrations were elevated in patients with MFS compared with control individuals (\n            <jats:italic>P<\/jats:italic>\n            &lt;0.0001; n=53; 15\u00b11.7 ng\/mL versus n=74; 2.5\u00b10.4 ng\/mL). MFS patients treated with losartan (n=55) or \u03b2-blocker (n=80) showed significantly lower total TGF-\u03b21 concentrations compared with untreated MFS patients (\n            <jats:italic>P<\/jats:italic>\n            \u22640.05).\n          <\/jats:p>\n          <jats:p>\n            <jats:bold>\n              <jats:italic>Conclusions\u2014<\/jats:italic>\n            <\/jats:bold>\n            Circulating TGF-\u03b21 concentrations are elevated in MFS and decrease after administration of losartan, \u03b2-blocker therapy, or both and therefore might serve as a prognostic and therapeutic marker in MFS.\n          <\/jats:p>","DOI":"10.1161\/circulationaha.108.841981","type":"journal-article","created":{"date-parts":[[2009,7,28]],"date-time":"2009-07-28T01:45:21Z","timestamp":1248745521000},"page":"526-532","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":240,"title":["Circulating Transforming Growth Factor-\u03b2 in Marfan Syndrome"],"prefix":"10.1161","volume":"120","author":[{"given":"Peter","family":"Matt","sequence":"first","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Schoenhoff","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Habashi","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy","family":"Holm","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christel","family":"Van Erp","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Loch","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga D.","family":"Carlson","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin F.","family":"Griswold","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qin","family":"Fu","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"De Backer","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bart","family":"Loeys","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Huso","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nazli B.","family":"McDonnell","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Van Eyk","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry C.","family":"Dietz","sequence":"additional","affiliation":[{"name":"From the Howard Hughes Medical Institute and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Md (P.M., F.S., J.H., T.H., C.V.E., D.L., H.C.D.); Division of Cardiac Surgery, University Hospital, Basel\/Berne, Switzerland (P.M.); Department of Cardiovascular Surgery, University of Berne, Switzerland (F.S.); Johns Hopkins Proteomics Center, Baltimore, Md (P.M., F.S., Q.F., J.E.V.E.); Laboratory of Clinical Investigation, National Institute on Aging, Bethesda, Md (O..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the GenTAC Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)67789-6"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/circulationaha.108.783753"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/352337a0"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtcvs.2007.08.047"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1116"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200422715"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1124287"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1536"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420641"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000182521.44440.c5"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0706585"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.echo.2005.10.005"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1006\/clin.1996.4308"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/stem.150190"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004410051364"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)80545-0"},{"key":"e_1_3_2_17_2","first-page":"II331","volume":"98","year":"1998","unstructured":"Segura AM, Luna RE, Horiba K, Stetler-Stevenson WG, McAllister HA Jr, Willerson JT, Ferrans VJ. Immunohistochemistry of matrix metalloproteinases and their inhibitors in thoracic aortic aneurysms and aortic valves of patients with Marfan\u2019s syndrome. Circulation. 1998; 98: II331\u2013II337.","journal-title":"Circulation"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320300405"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.298.13.1539"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehi492"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/circresaha.108.174367"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00578.2001"}],"container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/CIRCULATIONAHA.108.841981","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:02:30Z","timestamp":1715580150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/CIRCULATIONAHA.108.841981"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,8,11]]},"references-count":22,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2009,8,11]]}},"alternative-id":["10.1161\/CIRCULATIONAHA.108.841981"],"URL":"https:\/\/doi.org\/10.1161\/circulationaha.108.841981","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,8,11]]},"assertion":[{"value":"2009-07-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}