Capillary regression in vascular endothelial growth factor-deficient skeletal muscle.
Skeletal muscle angiogenesis is an important physiological adaptation to increased metabolic demand, possibly dependent on vascular endothelial growth factor (VEGF), the increased expression of which is a known early response to exercise. To test the hypothesis that VEGF is essential to muscle capillary maintenance, we evaluated the consequences of targeted skeletal muscle inhibition of VEGF expression in postnatal, cage-confined VEGFloxP(+/+) mice. To delete VEGF, cre recombinase expression was accomplished using direct intramuscular injection of a recombinant adeno-associated cre recombinase expressing viral vector. Four weeks postinfection, VEGF-inactivated regions revealed 64% decreases in capillary density and capillary-to-fiber ratio. Substantial apoptosis was also observed in VEGF-depleted regions. There was no evidence of rescue at 8 wk, with a persistent 67% reduction in capillary-to-fiber ratio and a 69% decrease in capillary density. These data implicate VEGF as an essential survival factor for muscle capillarity and also demonstrate insufficient VEGF-dependent signaling leads to apoptosis in mouse skeletal muscle.
Tang
Kechun
K
Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623, USA. ktang@ucsd.edu
Breen
Ellen C
EC
Gerber
Hans-Peter
HP
Ferrara
Napoleone M A
NM
Wagner
Peter D
PD
D000818:Animals; D017209:Apoptosis; D002196:Capillaries / Q000254:growth & development*; D000229:Dependovirus / Q000235:genetics; D017353:Gene Deletion; D018390:Gene Targeting; D005822:Genetic Vectors / Q000008:administration & dosage; D019426:Integrases / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018482:Muscle, Skeletal / Q000098:blood supply*; D018919:Neovascularization, Physiologic; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid; D042461:Vascular Endothelial Growth Factor A / Q000172:deficiency* / Q000235:genetics / Q000502:physiology; D014764:Viral Proteins / Q000235:genetics
D042461:Vascular Endothelial Growth Factor A; D014764:Viral Proteins; C045073:Cre recombinase; D019426:Integrases