Vascular endothelial growth factor stimulates skeletal muscle regeneration in Vivo

Nikola Arsic, Serena Zacchigna, Lorena Zentilin, Genaro Ramirez-Correa, Lucia Pattarini, Alessandro Salvi, Gianfranco Sinagra, Mauro Giacca

Research output: Contribution to journalArticle

Abstract

Vascular endothelial growth factor (VEGF) is a major regulator of blood vessel formation during development and in the adult organism. Recent evidence indicates that this factor also plays an important role in sustaining the proliferation and differentiation of different cell types, including progenitor cells of different tissues, including bone marrow, bone, and the central nervous system. Here we show that the delivery of the 165-aa isoform of VEGF-A cDNA using an adeno-associated virus (AAV) vector exerts a powerful effect on skeletal muscle regeneration in vivo. Following ischemia-, glycerol-, or cardiotoxin-induced damage in mouse skeletal muscle, the delivery of AAV-VEGF markedly improved muscle fiber reconstitution with a dose-dependent effect. The expression of both VEGF receptor-1 (VEGFR-1) and VEGFR-2 was upregulated both in the satellite cells of the damaged muscles and during myotube formation in vitro; the VEGF effect was mediated by the VEGFR-2, since the transfer of PlGF, a VEGF family member interacting with the VEGFR-1, was ineffective. These results are consistent with the observation that VEGF promotes the growth of myogenic fibers and protects the myogenic cells from apoptosis in vitro and prompt a therapeutic use for VEGF gene transfer in a variety of muscular disorders.

Original languageEnglish (US)
Pages (from-to)844-854
Number of pages11
JournalMolecular Therapy
Volume10
Issue number5
DOIs
StatePublished - Nov 1 2004

Keywords

  • Adeno-associated virus
  • Gene therapy
  • Muscle
  • Vascular endothelial growth factor
  • Vascular endothelial growth factor receptor-2

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

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  • Cite this

    Arsic, N., Zacchigna, S., Zentilin, L., Ramirez-Correa, G., Pattarini, L., Salvi, A., Sinagra, G., & Giacca, M. (2004). Vascular endothelial growth factor stimulates skeletal muscle regeneration in Vivo. Molecular Therapy, 10(5), 844-854. https://doi.org/10.1016/j.ymthe.2004.08.007