title: Structural and Functional Alterations of Skeletal Muscle Microvasculature in Dystrophin-Deficient mdx Mice.
abstract: Duchenne muscular dystrophy (DMD) is a progressive neuromuscular disease, caused by an absence of dystrophin, inevitably leading to death. Although muscle lesions are well characterized, blood vessel alterations that may have a major impact on muscle regeneration remain poorly understood. Our aim was to elucidate alterations of the vascular network organization, taking advantage of Flk1(GFP/+) crossed with mdx mice (model for human DMD where all blood vessels express green fluorescent protein) and functional repercussions using in vivo nuclear magnetic resonance, combining arterial spin-labeling imaging of perfusion, and (31)P-spectroscopy of phosphocreatine kinetics. For the first time, our study focused on old (12-month-old) mdx mice, displaying marked chronic muscle lesions, similar to the lesions observed in human DMD, in comparison to young-adult (3-month-old) mdx mice displaying only mild muscle lesions with no fibrosis. By using an original approach combining a specific animal model, state-of-the-art histology/morphometry techniques, and functional nuclear magnetic resonance, we demonstrated that the microvascular system is almost normal in young-adult in contrast to old mdx mice, displaying marked microvessel alterations, and the functional repercussions on muscle perfusion and bioenergetics after a hypoxic stress vary depending on stage of pathology. This original approach clarifies disease evolution and paves the way for setting up new diagnostic markers or therapeutic strategies.
authors.affiliation: Infection and Epidemiology Department, Human Histopathology and Animal Models, Institut Pasteur, Paris, France; The French Institute of Health and Medical Research (INSERM) U1016, Institut Cochin, Paris, France; The French National Centre for Scientific Research (CNRS) Unité Mixte de Recherche 8104, Paris, France; Paris Descartes University, Pôle de Recherche, Enseignement Supérieur Sorbonne-Paris-Cité, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Latroche
authors.affiliation: Nuclear Magnetic Resonance Laboratory, Institut de Myologie, Paris, France; Commissariat à l'énergie atomique, Institut d'Imagerie Biomédicale, Molecular Imaging Research Center, Institut de Myologie, NMR Laboratory, Paris, France.
authors.forename: Béatrice
authors.initials: B
authors.lastname: Matot
authors.affiliation: Nuclear Magnetic Resonance Laboratory, Institut de Myologie, Paris, France; Commissariat à l'énergie atomique, Institut d'Imagerie Biomédicale, Molecular Imaging Research Center, Institut de Myologie, NMR Laboratory, Paris, France; Laboratory of Muscle Proteins and Comparative Histology, Human Genome Research Center, Biosciences Institute, University of Sao Paulo, Sao Paulo, Brazil.
authors.forename: Aurea
authors.initials: A
authors.lastname: Martins-Bach
authors.affiliation: Infection and Epidemiology Department, Human Histopathology and Animal Models, Institut Pasteur, Paris, France.
authors.forename: David
authors.initials: D
authors.lastname: Briand
authors.affiliation: The French Institute of Health and Medical Research (INSERM) U1016, Institut Cochin, Paris, France; The French National Centre for Scientific Research (CNRS) Unité Mixte de Recherche 8104, Paris, France; Paris Descartes University, Pôle de Recherche, Enseignement Supérieur Sorbonne-Paris-Cité, Paris, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Chazaud
authors.affiliation: Nuclear Magnetic Resonance Laboratory, Institut de Myologie, Paris, France; Commissariat à l'énergie atomique, Institut d'Imagerie Biomédicale, Molecular Imaging Research Center, Institut de Myologie, NMR Laboratory, Paris, France.
authors.forename: Claire
authors.initials: C
authors.lastname: Wary
authors.affiliation: Nuclear Magnetic Resonance Laboratory, Institut de Myologie, Paris, France; Commissariat à l'énergie atomique, Institut d'Imagerie Biomédicale, Molecular Imaging Research Center, Institut de Myologie, NMR Laboratory, Paris, France.
authors.forename: Pierre G
authors.initials: PG
authors.lastname: Carlier
authors.affiliation: Infection and Epidemiology Department, Human Histopathology and Animal Models, Institut Pasteur, Paris, France; Paris Descartes University, Pôle de Recherche, Enseignement Supérieur Sorbonne-Paris-Cité, Paris, France; Neuropathology Department, Centre Hospitalier Sainte-Anne, Paris, France. Electronic address: fabrice.chretien@pasteur.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Chrétien
authors.affiliation: Infection and Epidemiology Department, Human Histopathology and Animal Models, Institut Pasteur, Paris, France; Paris Descartes University, Pôle de Recherche, Enseignement Supérieur Sorbonne-Paris-Cité, Paris, France.
authors.forename: Grégory
authors.initials: G
authors.lastname: Jouvion
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D016189:Dystrophin / Q000172:deficiency / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D055806:Microvessels / Q000378:metabolism / Q000473:pathology*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000378:metabolism* / Q000473:pathology*; D020388:Muscular Dystrophy, Duchenne / Q000378:metabolism* / Q000473:pathology
chemical_list: D016189:Dystrophin