{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:36:52Z","timestamp":1792233412876,"version":"4.4.0"},"reference-count":74,"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>Marfan\u2019s syndrome is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix microfibrils and chronic tissue growth factor (TGF)-\u03b2 signaling. TGF-\u03b2 is a potent regulator of the vascular smooth muscle cell (VSMC) phenotype. We hypothesized that as a result of the chronic TGF-\u03b2 signaling, VSMC would alter their basal differentiation phenotype, which could facilitate the formation of aneurysms. This study explores whether Marfan\u2019s syndrome entails phenotypic alterations of VSMC and possible mechanisms at the subcellular level.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>Immunohistochemical and Western blotting analyses of dilated aortas from Marfan patients showed overexpression of contractile protein markers (\u03b1-smooth muscle actin, smoothelin, smooth muscle protein 22 alpha, and calponin-1) and collagen I in comparison with healthy aortas. VSMC explanted from Marfan aortic aneurysms showed increased in vitro expression of these phenotypic markers and also of myocardin, a transcription factor essential for VSMC-specific differentiation. These alterations were generally reduced after pharmacological inhibition of the TGF-\u03b2 pathway. Marfan VSMC in culture showed more robust actin stress fibers and enhanced RhoA-GTP levels, which was accompanied by increased focal adhesion components and higher nuclear localization of myosin-related transcription factor A. Marfan VSMC and extracellular matrix measured by atomic force microscopy were both stiffer than their respective controls.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>In Marfan VSMC, both in tissue and in culture, there are variable TGF-\u03b2-dependent phenotypic changes affecting contractile proteins and collagen I, leading to greater cellular and extracellular matrix stiffness. Altogether, these alterations may contribute to the known aortic rigidity that precedes or accompanies Marfan\u2019s syndrome aneurysm formation.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.114.304412","type":"journal-article","created":{"date-parts":[[2015,1,16]],"date-time":"2015-01-16T04:07:22Z","timestamp":1421381242000},"page":"960-972","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":142,"title":["Vascular Smooth Muscle Cell Phenotypic Changes in Patients With Marfan Syndrome"],"prefix":"10.1161","volume":"35","author":[{"given":"Eva","family":"Crosas-Molist","sequence":"first","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thayna","family":"Meirelles","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judit","family":"L\u00f3pez-Luque","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carla","family":"Serra-Peinado","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Selva","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Caja","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darya","family":"Gorbenko del Blanco","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Uriarte","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Bertran","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Mendiz\u00e1bal","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Garc\u00eda-Calero","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oscar","family":"Busnadiego","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enric","family":"Condom","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Toral","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manel","family":"Castell\u00e0","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Forteza","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Navajas","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; Institut d\u2019Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanoci\u00e8ncia i Nanotecnologia (IN2UB), Barcelona,..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabet","family":"Sarri","sequence":"additional","affiliation":[{"name":"From the Department of Cell Biology, Immunology and Neurosciences (E.C.-M., T.M., C.S.-P, J.S., D.G, Y.M., V.H., E.S., G.E.), Departments of Physiological Sciences I (J.J.U., D.N.) and Physiological Sciences II (I.F.), Department of Pathology and Experimental Therapeutics (E.C.), University of Barcelona School of Medicine, Barcelona, Spain; 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