Adeno-associated virus serotype 9 mediated vascular endothelial growth factor gene overexpression in mdx mice

Abstract

Duchenne muscular dystrophy (DMD) is a fatal neuromuscular disease caused by the absence of dystrophin. Vascular endothelial growth factor (VEGF) is a heparin-binding dimeric glycoprotein and principal angiogenic factor stimulating the migration, proliferation and expression of various genes in endothelial cells. Recently, VEGF was demonstrated to exhibit an antiapoptotic and direct myogenic effect, as well as to enhance muscle force restoration subsequent to traumatic injury. Therefore, the present study attempted to assess the muscle damage of VEGF overexpression in mdx mice. Adeno-associated virus serotype 9 (AAV9)-VEGF was administered intravenously to mdx mice. At 4 weeks after injection, VEGF was observed to be upregulated in the tibialis anterior muscle. In addition, the serum creatine kinase levels were significantly reduced and fatigue was slowed down, whereas the limb grip strength and weight of mice were markedly increased compared with the saline-treated mdx mice. Furthermore, significantly reduced inflammation and necrosis areas were observed in the muscle tissues of mice in the AAV9-VEGF group. These results suggested that AAV9-mediated VEGF gene overexpression was able to improve the muscle damage in mdx mice.