Résumé :
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Communication n° 282 Introduction : As blood vessels represent a promising route to deliver therapeutic genes or cells to dystrophic muscle, the question arises whether dystrophin deficiency is associated with impaired muscular vascularization, as previously shown in the X-linked muscular dystrophy mouse. The study was performed in the closest animal model of Duchenne Muscular Dystrophy, the GRMD (golden retriever muscular dystrophy) dog. Objectives : To determine the nature and severity of microvessel anomalies in GRMD muscles, and their correlations with muscle lesions. Methods : The gracilis and sartorius cranialis muscles were sampled in 1- to 3-month-old GRMD (n=4) and control (n=6) dogs. Automated morphometry was used on von-Willebrand-factor immunostained sections to quantify microvessel density. Manual morphometry was used on semi-thin sections to quantify muscle fibrosis and myofibre size; and on ultra-thin sections to assess the ultrastructure of blood capillaries. Results : Microvessel density was unaltered in GRMD gracilis muscle (758Æ198 /mm2) compared to control one (764Æ54 /mm2). There was capillary hypertrophy (microvessel diameter, 3.9 µm vs 3.2 in controls), with a normal endothelium area (64Æ18% vs 70Æ17% in controls), and normal lumen area (29Æ18% versus 23Æ18% in controls). GRMD microvessels showed thickened basement membrane (81Æ16 nm versus 65Æ11 nm in controls). Fibrosis in GRMD dogs (14Æ4% versus 7Æ3% in controls) correlated with increased frequency of basement membrane duplication (56% versus 14% in controls), decreased number of myofibres adjacent to a microvessel, and increased distance from microvessel to myofibre (541Æ551 nm versus 158Æ168 in controls). Similar results were found in the sartorius cranialis muscle (P < 0.05 for all results). Conclusion : Microvasculature is impaired in GRMD skeletal muscles, as soon as three months of age. The increased capillary-to-myofibre distance correlates with endomysial fibrosis and may impede intravascular therapeutic trials.
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