Capillary regression in vascular endothelial growth factor-deficient skeletal muscle

1 Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623 2 Department of Molecular Oncology, Genentech, Incorporated, South San Francisco, California Skeletal muscle angiogenesis is an important physiological adaptation to increased metab...

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Published in:Physiological genomics 2004-06, Vol.18 (1), p.63-69
Main Authors: Tang, Kechun, Breen, Ellen C, Gerber, Hans-Peter, Ferrara, Napoleone M. A, Wagner, Peter D
Format: Article
Language:English
Subjects:
Adeno-associated virus
Animals
Apoptosis
Capillaries - growth & development
Dependovirus - genetics
Gene Deletion
Gene Targeting
Genetic Vectors - administration & dosage
Integrases - genetics
Mice
Mice, Inbred C57BL
Mice, Transgenic
Muscle, Skeletal - blood supply
Neovascularization, Physiologic
Recombination, Genetic
Regulatory Sequences, Nucleic Acid
Vascular Endothelial Growth Factor A - deficiency
Vascular Endothelial Growth Factor A - genetics
Vascular Endothelial Growth Factor A - physiology
Viral Proteins - genetics
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Summary:1 Division of Physiology, Department of Medicine, University of California, San Diego, La Jolla, California 92093-0623 2 Department of Molecular Oncology, Genentech, Incorporated, South San Francisco, California 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 VEGF loxP (+/+) 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. muscle; apoptosis; capillaries; peripheral vascular disease; growth factors/cytokines
ISSN:1094-8341
1531-2267
DOI:10.1152/physiolgenomics.00023.2004