title: Vascular smooth muscle cell phenotypic changes in patients with Marfan syndrome.
abstract: OBJECTIVE
  Marfan's syndrome is characterized by the formation of ascending aortic aneurysms resulting from altered assembly of extracellular matrix microfibrils and chronic tissue growth factor (TGF)-β signaling. TGF-β is a potent regulator of the vascular smooth muscle cell (VSMC) phenotype. We hypothesized that as a result of the chronic TGF-β signaling, VSMC would alter their basal differentiation phenotype, which could facilitate the formation of aneurysms. This study explores whether Marfan's syndrome entails phenotypic alterations of VSMC and possible mechanisms at the subcellular level.
  
  
  RESULTS
  Immunohistochemical and Western blotting analyses of dilated aortas from Marfan patients showed overexpression of contractile protein markers (α-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-β 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.
  
  
  CONCLUSIONS
  In Marfan VSMC, both in tissue and in culture, there are variable TGF-β-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's syndrome aneurysm formation.
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Eva
authors.initials: E
authors.lastname: Crosas-Molist
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Thayna
authors.initials: T
authors.lastname: Meirelles
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Judit
authors.initials: J
authors.lastname: López-Luque
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Carla
authors.initials: C
authors.lastname: Serra-Peinado
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Javier
authors.initials: J
authors.lastname: Selva
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Laia
authors.initials: L
authors.lastname: Caja
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Darya
authors.initials: D
authors.lastname: Gorbenko Del Blanco
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Juan José
authors.initials: JJ
authors.lastname: Uriarte
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Esther
authors.initials: E
authors.lastname: Bertran
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Mendizábal
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Vanessa
authors.initials: V
authors.lastname: Hernández
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Carolina
authors.initials: C
authors.lastname: García-Calero
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Oscar
authors.initials: O
authors.lastname: Busnadiego
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Enric
authors.initials: E
authors.lastname: Condom
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: David
authors.initials: D
authors.lastname: Toral
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Manel
authors.initials: M
authors.lastname: Castellà
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Alberto
authors.initials: A
authors.lastname: Forteza
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Daniel
authors.initials: D
authors.lastname: Navajas
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Elisabet
authors.initials: E
authors.lastname: Sarri
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Fernando
authors.initials: F
authors.lastname: Rodríguez-Pascual
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Harry C
authors.initials: HC
authors.lastname: Dietz
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.).
authors.forename: Isabel
authors.initials: I
authors.lastname: Fabregat
authors.affiliation: 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'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (M.C., G.E.); Institut de Nanociència i Nanotecnologia (IN2UB), Barcelona, Spain (G.E.); Institut de Bioenginyeria de Catalunya (IBEC), Barcelona, Spain and CIBER de Enfermedades Respiratorias (CIBERES) (D.N.); Vascular Biology Laboratory, Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, Brazil (T.M.); Institut d'Investigació Biomèdica de Bellvitge (IDIBELL), L'Hospitalet de Llobregat, Barcelona, Spain (E.C.-M., J.L.-L. L.C., E.B., I.F.); Centro de Biología Molecular Severo Ochoa (CSIC-UAM), Madrid, Spain (O.B., F.R.-P.); Hospital de Bellvitge-IDIBELL, L'Hospitalet de Llobregat, Barcelona, Spain (C.G.-C., E.C., D.T.); Cardiovascular Surgery Department, Hospital Clínic i Provincial, Barcelona, Spain (M.C.); Cardiac Surgery Department, Marfan Syndrome Unit, Hospital Universitario 12 de Octubre, Madrid, Spain (A.F.); and William S. Smilow Center for Marfan Syndrome Research, Howard Hughes Medical Institute, Johns Hopkins University School of Medicine, Baltimore, MD (H.C.D.). gegea@ub.edu.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Egea
mesh_terms: D000199:Actins / Q000378:metabolism; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001014:Aortic Aneurysm / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism; D016022:Case-Control Studies; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D024042:Collagen Type I / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004108:Dilatation, Pathologic; D022001:Focal Adhesions / Q000378:metabolism; D006801:Humans; D008382:Marfan Syndrome / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D008840:Microfilament Proteins / Q000378:metabolism; D009124:Muscle Proteins / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D010641:Phenotype; D015398:Signal Transduction; D022502:Stress Fibers / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism; D066253:Vascular Remodeling; D020742:rhoA GTP-Binding Protein / Q000378:metabolism; D000096985:Calponins; D000099251:Myocardin
chemical_list: D000199:Actins; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D024042:Collagen Type I; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D009124:Muscle Proteins; D009687:Nuclear Proteins; D015534:Trans-Activators; D016212:Transforming Growth Factor beta; D020742:rhoA GTP-Binding Protein; D000096985:Calponins; D000099251:Myocardin; C541116:ACTA2 protein, human; C100762:SMTN protein, human; C051615:transgelin; C066737:RHOA protein, human
keywords: RhoA; TGF-β; actin; aortic aneurysms; aortic stiffness; extracellular matrix; focal adhesion; myocardin