{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T10:05:08Z","timestamp":1791021908698,"version":"4.1.0"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2007,8,31]]},"abstract":"<jats:p>\n            Thoracic aortic aneurysm (TAA) is the life-threatening complication of Marfan syndrome (MFS), a connective tissue disorder caused by mutations in the fibrillin-1 gene. TAA is characterized by degradation of elastic fiber, suggesting the involvement of matrix metalloproteinase (MMP)-2 and -9, the activation of which is regulated by TIMP (tissue inhibitor of MMP) types 1 and 2. We hypothesized that MMP-2 and -9 were upregulated during TAA formation in Marfan syndrome, causing loss of elastic fibers and structural integrity. We studied mice, from 3 to 12 months, heterozygous for a mutant\n            <jats:italic>Fbn<\/jats:italic>\n            1 allele encoding a cysteine substitution in fibrillin-1 (\n            <jats:italic>Fbn1<\/jats:italic>\n            <jats:sup>C1039G\/+<\/jats:sup>\n            , designated as \u201cMarfan\u201d mice) (n=120), the most common class of mutation in Marfan syndrome. The littermates,\n            <jats:italic>Fbn1<\/jats:italic>\n            <jats:sup>+\/+<\/jats:sup>\n            served as controls (n=120). In Marfan aneurysmal thoracic aorta, mRNA and protein expression of MMP-2 and -9 were detected at 3 months and peaked at 6 months of age, accompanied by severe elastic fiber fragmentation and degradation. From 3 to 9 months, the MMP-2\/TIMP-2 ratio increased by 43% to 63% compared with the controls. Dilated thoracic aorta demonstrated increased elasticity but distention caused a pronounced loss of contraction, suggesting weakening of the aortic wall. Breaking stress of the aneurysmal aorta was 70% of the controls. Contraction in response to depolarization and receptor stimulation decreased in the aneurysmal thoracic aorta by 50% to 80%, but the expression of \u03b1-smooth muscle actin between the 2 strains was not significantly different. This report demonstrates the upregulation of MMP-2 and -9 during TAA formation in Marfan syndrome. The resulting elastic fiber degeneration with deterioration of the aortic contraction and mechanical properties may explain the pathogenesis of TAA.\n          <\/jats:p>","DOI":"10.1161\/circresaha.107.157776","type":"journal-article","created":{"date-parts":[[2007,7,20]],"date-time":"2007-07-20T01:14:51Z","timestamp":1184894091000},"page":"512-522","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":214,"title":["Loss of Elastic Fiber Integrity and Reduction of Vascular Smooth Muscle Contraction Resulting From the Upregulated Activities of Matrix Metalloproteinase-2 and -9 in the Thoracic Aortic Aneurysm in Marfan Syndrome"],"prefix":"10.1161","volume":"101","author":[{"given":"Ada W.Y.","family":"Chung","sequence":"first","affiliation":[{"name":"From the Child and Family Research Institute (A.W.Y.C., K.A.Y., C.v.B.) and Department of Anesthesiology, Pharmacology and Therapeutics (A.W.Y.C., K.A.Y., C.v.B.); Division of Cardiology (G.G.S.S.), Department of Pediatrics, British Columbia Children\u2019s Hospital, University of British Columbia, Vancouver, Canada; and Howard Hughes Medical Institute and the Institute of Genetic Medicine (D.P.J., H.C.D.), Johns Hopkins University School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Au Yeung","sequence":"additional","affiliation":[{"name":"From the Child and Family Research Institute (A.W.Y.C., K.A.Y., C.v.B.) and Department of Anesthesiology, Pharmacology and Therapeutics (A.W.Y.C., K.A.Y., C.v.B.); Division of Cardiology (G.G.S.S.), Department of Pediatrics, British Columbia Children\u2019s Hospital, University of British Columbia, Vancouver, Canada; and Howard Hughes Medical Institute and the Institute of Genetic Medicine (D.P.J., H.C.D.), Johns Hopkins University School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George G.S.","family":"Sandor","sequence":"additional","affiliation":[{"name":"From the Child and Family Research Institute (A.W.Y.C., K.A.Y., C.v.B.) and Department of Anesthesiology, Pharmacology and Therapeutics (A.W.Y.C., K.A.Y., C.v.B.); Division of Cardiology (G.G.S.S.), Department of Pediatrics, British Columbia Children\u2019s Hospital, University of British Columbia, Vancouver, Canada; and Howard Hughes Medical Institute and the Institute of Genetic Medicine (D.P.J., H.C.D.), Johns Hopkins University School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel P.","family":"Judge","sequence":"additional","affiliation":[{"name":"From the Child and Family Research Institute (A.W.Y.C., K.A.Y., C.v.B.) and Department of Anesthesiology, Pharmacology and Therapeutics (A.W.Y.C., K.A.Y., C.v.B.); Division of Cardiology (G.G.S.S.), Department of Pediatrics, British Columbia Children\u2019s Hospital, University of British Columbia, Vancouver, Canada; and Howard Hughes Medical Institute and the Institute of Genetic Medicine (D.P.J., H.C.D.), Johns Hopkins University School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry C.","family":"Dietz","sequence":"additional","affiliation":[{"name":"From the Child and Family Research Institute (A.W.Y.C., K.A.Y., C.v.B.) and Department of Anesthesiology, Pharmacology and Therapeutics (A.W.Y.C., K.A.Y., C.v.B.); Division of Cardiology (G.G.S.S.), Department of Pediatrics, British Columbia Children\u2019s Hospital, University of British Columbia, Vancouver, Canada; and Howard Hughes Medical Institute and the Institute of Genetic Medicine (D.P.J., H.C.D.), Johns Hopkins University School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cornelis","family":"van Breemen","sequence":"additional","affiliation":[{"name":"From the Child and Family Research Institute (A.W.Y.C., K.A.Y., C.v.B.) and Department of Anesthesiology, Pharmacology and Therapeutics (A.W.Y.C., K.A.Y., C.v.B.); Division of Cardiology (G.G.S.S.), Department of Pediatrics, British Columbia Children\u2019s Hospital, University of British Columbia, Vancouver, Canada; and Howard Hughes Medical Institute and the Institute of Genetic Medicine (D.P.J., H.C.D.), Johns Hopkins University School of Medicine, Baltimore, Md."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_3_1_2","first-page":"1965","volume":"366","year":"2000","unstructured":"Judge DP, Dietz HC. 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