{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:07:59Z","timestamp":1791331679982,"version":"4.3.1"},"reference-count":31,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2012,1,20]]},"abstract":"<jats:sec>\n            <jats:title>\n              <jats:underline>Rationale:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>Marfan syndrome (MFS) is a systemic connective tissue disorder notable for the development of aortic root aneurysms and the subsequent life-threatening complications of aortic dissection and rupture. Underlying fibrillin-1 gene mutations cause increased transforming growth factor-\u03b2 (TGF-\u03b2) signaling. Although TGF-\u03b2 blockade prevents aneurysms in MFS mouse models, the mechanisms through which excessive TGF-\u03b2 causes aneurysms remain ill-defined.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Objective:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We investigated the role of microRNA-29b (miR-29b) in aneurysm formation in MFS.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Methods and Results:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>\n              Using quantitative polymerase chain reaction, we discovered that miR-29b, a microRNA regulating apoptosis and extracellular matrix synthesis\/deposition genes, is increased in the ascending aorta of Marfan (\n              <jats:italic>Fbn1<\/jats:italic>\n              <jats:sup>C1039G\/+<\/jats:sup>\n              ) mice. Increased apoptosis, assessed by increased cleaved caspase-3 and caspase-9, enhanced caspase-3 activity, and decreased levels of the antiapoptotic proteins, Mcl-1 and Bcl-2, were found in the\n              <jats:italic>Fbn1<\/jats:italic>\n              <jats:sup>C1039G\/+<\/jats:sup>\n              aorta. Histological evidence of decreased and fragmented elastin was observed exclusively in the\n              <jats:italic>Fbn1<\/jats:italic>\n              <jats:sup>C1039G\/+<\/jats:sup>\n              ascending aorta in association with repressed elastin mRNA and increased matrix metalloproteinase-2 expression and activity, both targets of miR-29b. Evidence of decreased activation of nuclear factor \u03baB, a repressor of miR-29b, and a factor suppressed by TGF-\u03b2, was also observed in\n              <jats:italic>Fbn1<\/jats:italic>\n              <jats:sup>C1039G\/+<\/jats:sup>\n              aorta. Furthermore, administration of a nuclear factor \u03baB inhibitor increased miR-29b levels, whereas TGF-\u03b2 blockade or losartan effectively decreased miR-29b levels in\n              <jats:italic>Fbn1<\/jats:italic>\n              <jats:sup>C1039G\/+<\/jats:sup>\n              mice. Finally, miR-29b blockade by locked nucleic acid antisense oligonucleotides prevented early aneurysm development, aortic wall apoptosis, and extracellular matrix deficiencies.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>\n              <jats:underline>Conclusions:<\/jats:underline>\n            <\/jats:title>\n            <jats:p>We identify increased miR-29b expression as key to the pathogenesis of early aneurysm development in MFS by regulating aortic wall apoptosis and extracellular matrix abnormalities.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.111.253740","type":"journal-article","created":{"date-parts":[[2011,11,24]],"date-time":"2011-11-24T07:20:29Z","timestamp":1322119229000},"page":"312-324","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":170,"title":["miR-29b Participates in Early Aneurysm Development in Marfan Syndrome"],"prefix":"10.1161","volume":"110","author":[{"given":"Denis R.","family":"Merk","sequence":"first","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jocelyn T.","family":"Chin","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A.","family":"Dake","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Maegdefessel","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miquell O.","family":"Miller","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoyuki","family":"Kimura","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip S.","family":"Tsao","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristiana","family":"Iosef","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerald J.","family":"Berry","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich W.","family":"Mohr","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua M.","family":"Spin","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina M.","family":"Alvira","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; Department of Cardiothoracic Surgery (D.R.M., F.W.M.), Heart Center Leipzig, Leipzig, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert C.","family":"Robbins","sequence":"additional","affiliation":[{"name":"From the Department of Cardiothoracic Surgery (D.R.M., J.T.C., B.A.D., M.O.M., N.K., R.C.R., M.P.F.), Department of Pediatrics (C.I., C.M.A.), Department of Cardiovascular Medicine (L.M., P.S.T., J.M.S.), Department of Pathology (G.J.B.), Stanford University, Stanford, CA; 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