TY - JOUR
T1 - Vascular endothelial growth factor stimulates skeletal muscle regeneration in Vivo
AU - Arsic, Nikola
AU - Zacchigna, Serena
AU - Zentilin, Lorena
AU - Ramirez-Correa, Genaro
AU - Pattarini, Lucia
AU - Salvi, Alessandro
AU - Sinagra, Gianfranco
AU - Giacca, Mauro
N1 - Funding Information:
This work was supported by grants from the Progetto Finalizzato bGenetica MolecolareQ of the Consiglio Nazionale delle Ricerche, Italy; from the FIRB program of the Ministero dell’Istruzione, Universita’ e Ricerca, Italy; and from the Fondazione Cassa di Risparmio of Trieste, Italy. We are very grateful to Barbara Boziglav and Mauro Sturnega for excellent technical support and to Suzanne Kerbavcic for editorial assistance.
PY - 2004/11
Y1 - 2004/11
N2 - 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.
AB - 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.
KW - Adeno-associated virus
KW - Gene therapy
KW - Muscle
KW - Vascular endothelial growth factor
KW - Vascular endothelial growth factor receptor-2
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U2 - 10.1016/j.ymthe.2004.08.007
DO - 10.1016/j.ymthe.2004.08.007
M3 - Article
C2 - 15509502
AN - SCOPUS:7044235846
SN - 1525-0016
VL - 10
SP - 844
EP - 854
JO - Molecular Therapy
JF - Molecular Therapy
IS - 5
ER -