title: Early Impairment of Lung Mechanics in a Murine Model of Marfan Syndrome.
abstract: Early morbidity and mortality in patients with Marfan syndrome (MFS) -a connective tissue disease caused by mutations in fibrillin-1 gene- are mainly caused by aorta aneurysm and rupture. However, the increase in the life expectancy of MFS patients recently achieved by reparatory surgery promotes clinical manifestations in other organs. Although some studies have reported respiratory alterations in MFS, our knowledge of how this connective tissue disease modifies lung mechanics is scarce. Hence, we assessed whether the stiffness of the whole lung and of its extracellular matrix (ECM) is affected in a well-characterized MFS mouse model (FBN1C1039G/+). The stiffness of the whole lung and of its ECM were measured by conventional mechanical ventilation and atomic force microscopy, respectively. We studied 5-week and 9-month old mice, whose ages are representative of early and late stages of the disease. At both ages, the lungs of MFS mice were significantly more compliant than in wild type (WT) mice. By contrast, no significant differences were found in local lung ECM stiffness. Moreover, histopathological lung evaluation showed a clear emphysematous-like pattern in MFS mice since alveolar space enlargement was significantly increased compared with WT mice. These data suggest that the mechanism explaining the increased lung compliance in MFS is not a direct consequence of reduced ECM stiffness, but an emphysema-like alteration in the 3D structural organization of the lung. Since lung alterations in MFS are almost fully manifested at an early age, it is suggested that respiratory monitoring could provide early biomarkers for diagnosis and/or follow-up of patients with the Marfan syndrome.
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|CIBER Enfermedades Respiratorias, Madrid, Spain.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Uriarte
authors.affiliation: Departament de Biologia Cel·lular, Immunologia i Neurociències, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Thayna
authors.initials: T
authors.lastname: Meirelles
authors.affiliation: Departament de Biologia Cel·lular, Immunologia i Neurociències, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Darya
authors.initials: D
authors.lastname: Gorbenko Del Blanco
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|Master's and Doctoral Degree Programs in Rehabilitation Sciences, Nove de Julho University, Sao Paulo, Brazil.
authors.forename: Paula N
authors.initials: PN
authors.lastname: Nonaka
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|CIBER Enfermedades Respiratorias, Madrid, Spain.|Institut de Bioenginyeria de Catalunya, Barcelona, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Campillo
authors.affiliation: Departament de Biologia Cel·lular, Immunologia i Neurociències, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Sarri
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|CIBER Enfermedades Respiratorias, Madrid, Spain.|Institut de Bioenginyeria de Catalunya, Barcelona, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Navajas
authors.affiliation: Departament de Biologia Cel·lular, Immunologia i Neurociències, Universitat de Barcelona, Barcelona, Spain.|Institut de Nanociències i Nanotecnologia, Universitat de Barcelona, Barcelona, Spain.|Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Egea
authors.affiliation: Unitat Biofísica i Bioenginyeria, Facultat de Medicina, Universitat de Barcelona, Barcelona, Spain.|CIBER Enfermedades Respiratorias, Madrid, Spain.|Institut d'Investigacions Biomèdiques August Pi Sunyer, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Farré
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000235:genetics / Q000473:pathology; D000071838:Fibrillin-1; D000071837:Fibrillins; D008168:Lung / Q000473:pathology*; D008382:Marfan Syndrome / Q000235:genetics / Q000473:pathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics; D009154:Mutation / Q000235:genetics; D054392:Adipokines
chemical_list: D000071838:Fibrillin-1; D000071837:Fibrillins; D008840:Microfilament Proteins; C000605724:Fbn1 protein, mouse; D054392:Adipokines