title: Enhanced arteriogenesis and wound repair in dystrophin-deficient mdx mice.
abstract: BACKGROUND
  The absence of functional dystrophin in Duchenne muscular dystrophy (DMD) patients and in mdx mice results in progressive muscle degeneration associated with necrosis, fibrosis, and inflammation. Because vascular supply plays a key role in tissue repair, we examined whether new blood vessel development was altered in mdx mice.
  
  
  RESULTS
  In a model of hindlimb ischemia on femoral artery dissection, hindlimb perfusion, measured by laser Doppler imaging, was higher in mdx mice (0.67+/-0.26) than in wild-type (WT) mice (0.33+/-0.18, P<0.03). In keeping with these data, a significant increase in arteriole length density was found in mdx mice (13.6+/-8.4 mm/mm3) compared with WT mice (7.8+/-4.6 mm/mm3, P<0.03). Conversely, no difference was observed in capillary density between mice of the 2 genotypes. The enhanced regenerative response was not limited to ischemic skeletal muscle, because in a wound-healing assay, mdx mice showed an accelerated wound closure rate compared with WT mice. Moreover, a vascularization assay in Matrigel plugs containing basic fibroblast growth factor injected subcutaneously revealed an increased length density of arterioles in mdx (46.9+/-14.7 mm/mm3) versus WT mice (19.5+/-5.8 mm/mm3, P<0.001). Finally, serum derived from mdx mice sustained formation of endothelium-derived tubular structures in vitro more efficiently than WT serum.
  
  
  CONCLUSIONS
  These results demonstrate that arteriogenesis is enhanced in mdx mice both after ischemia and skin wounding and in response to growth factors.
authors.affiliation: Laboratorio di Biologia Vascolare e Terapia Genica, Centro Cardiologico I, Monzino, IRCCS, Milan, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Straino
authors.forename: Antonia
authors.initials: A
authors.lastname: Germani
authors.forename: Anna
authors.initials: A
authors.lastname: Di Carlo
authors.forename: Daniele
authors.initials: D
authors.lastname: Porcelli
authors.forename: Roberta
authors.initials: R
authors.lastname: De Mori
authors.forename: Antonella
authors.initials: A
authors.lastname: Mangoni
authors.forename: Monica
authors.initials: M
authors.lastname: Napolitano
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
authors.forename: Paolo
authors.initials: P
authors.lastname: Biglioli
authors.forename: Maurizio C
authors.initials: MC
authors.lastname: Capogrossi
mesh_terms: D000818:Animals; D001160:Arterioles / Q000648:ultrastructure; D002196:Capillaries / Q000648:ultrastructure; D003094:Collagen; D003114:Colony-Forming Units Assay; D004338:Drug Combinations; D016189:Dystrophin / Q000502:physiology*; D005263:Femoral Artery / Q000293:injuries; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage / Q000494:pharmacology; D019650:Hematopoietic Stem Cell Mobilization; D006614:Hindlimb / Q000098:blood supply*; D007511:Ischemia / Q000503:physiopathology*; D007797:Laminin; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018482:Muscle, Skeletal / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology*; D011509:Proteoglycans; D012038:Regeneration; D014945:Wound Healing / Q000502:physiology*
chemical_list: D004338:Drug Combinations; D016189:Dystrophin; D007797:Laminin; D011509:Proteoglycans; D016222:Fibroblast Growth Factor 2; C059485:matrigel; D003094:Collagen