title: VEGF overexpression via adeno-associated virus gene transfer promotes skeletal muscle regeneration and enhances muscle function in mdx mice.
abstract: Vascular endothelial growth factor (VEGF) is a major regulator of physiological and pathological angiogenesis. Recently it was reported that the delivery of VEGF using recombinant adeno-associated virus (rAAV) vectors reduces muscle damage and promotes muscle regeneration in different experimental models of muscle necrosis. We demonstrate that intramuscular administration of rAAV-VEGF improved pathophysiology of the mdx mouse, a model of Duchenne muscular dystrophy (DMD). One month after injection, rAAV-VEGF-treated muscles showed augmented expression of VEGF and immunolocalization of its receptor, VEGFR-2. VEGF-treated mdx mice showed increased forelimb strength and strength normalized to weight. Treatment reduced necrotic fibers area and increased regenerating fibers area with an augmented number of myogenin-positive satellite cells and myonuclei, and of developmental myosin heavy chain-positive fibers. Only the regenerating area showed increased capillary density. This study provides novel evidence of a VEGF beneficial effect in mdx mice that is exerted mainly by a proregenerative and angiogenic effect. It opens new therapeutic prospectives in DMD and other types of muscular disorders.
authors.affiliation: Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Italy.
authors.forename: Sonia
authors.initials: S
authors.lastname: Messina
authors.forename: Anna
authors.initials: A
authors.lastname: Mazzeo
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bitto
authors.forename: M'hammed
authors.initials: M
authors.lastname: Aguennouz
authors.forename: Alba
authors.initials: A
authors.lastname: Migliorato
authors.forename: Maria G
authors.initials: MG
authors.lastname: De Pasquale
authors.forename: Letteria
authors.initials: L
authors.lastname: Minutoli
authors.forename: Domenica
authors.initials: D
authors.lastname: Altavilla
authors.forename: Lorena
authors.initials: L
authors.lastname: Zentilin
authors.forename: Mauro
authors.initials: M
authors.lastname: Giacca
authors.forename: Francesco
authors.initials: F
authors.lastname: Squadrito
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Vita
mesh_terms: D000818:Animals; D000229:Dependovirus / Q000235:genetics*; D018014:Gene Transfer Techniques; D051379:Mice; D018482:Muscle, Skeletal / Q000503:physiopathology*; D009136:Muscular Dystrophies / Q000235:genetics* / Q000503:physiopathology; D012038:Regeneration / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
chemical_list: D042461:Vascular Endothelial Growth Factor A