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: Sonia Messina, Anna Mazzeo, Alessandra Bitto, M'hammed Aguennouz, Alba Migliorato, Maria G De Pasquale, Letteria Minutoli, Domenica Altavilla, Lorena Zentilin, Mauro Giacca, Francesco Squadrito, Giuseppe Vita
• Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology (FASEB J) Vol. 21 Issue 13 Pg. 3737-46 (Nov 2007) ISSN: 1530-6860 [Electronic] United States
• PMID: 17575261 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Vascular Endothelial Growth Factor A

Topics

• Animals
• Dependovirus (genetics)
• Gene Transfer Techniques
• Mice
• Muscle, Skeletal (physiopathology)
• Muscular Dystrophies (genetics, physiopathology)
• Regeneration (genetics)
• Vascular Endothelial Growth Factor A (genetics, metabolism)