Structural and Functional Alterations of Skeletal Muscle Microvasculature in Dystrophin-Deficient mdx Mice. - Institut Pasteur Access content directly
Journal Articles American Journal of Pathology Year : 2015

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.
Fichier principal
Vignette du fichier
Latroche_Am J Pathol_2015.pdf (9.02 Mo) Télécharger le fichier
Origin : Files produced by the author(s)
Loading...

Dates and versions

pasteur-01151848 , version 1 (13-05-2015)

Licence

Attribution - NonCommercial

Identifiers

Cite

Claire Latroche, Béatrice Matot, Aurea Martins-Bach, David Briand, Bénédicte Chazaud, et al.. Structural and Functional Alterations of Skeletal Muscle Microvasculature in Dystrophin-Deficient mdx Mice.. American Journal of Pathology, 2015, 185 (9), pp.2482-94. ⟨10.1016/j.ajpath.2015.05.009⟩. ⟨pasteur-01151848⟩
270 View
323 Download

Altmetric

Share

Gmail Facebook X LinkedIn More