VEGF overexpression via adeno-associated virus gene transfer promotes skeletal muscle regeneration and enhances muscle function in mdx mice.
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.
Messina
Sonia
S
Department of Neurosciences, Psychiatry and Anaesthesiology, University of Messina, Italy.
Mazzeo
Anna
A
Bitto
Alessandra
A
Aguennouz
M'hammed
M
Migliorato
Alba
A
De Pasquale
Maria G
MG
Minutoli
Letteria
L
Altavilla
Domenica
D
Zentilin
Lorena
L
Giacca
Mauro
M
Squadrito
Francesco
F
Vita
Giuseppe
G
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*
D042461:Vascular Endothelial Growth Factor A