VEGF gene delivery to muscle: potential role for vasculogenesis in adults.
Constitutive expression of VEGF after implantation of genetically engineered myoblasts into non-ischemic muscle led to an increase in vascular structures. Previously, effects of VEGF delivery to adult muscle have only been reported in ischemic tissues. The resulting vascular structures were reminiscent of those formed during embryonic vasculogenesis, rather than angiogenesis, sprouting from preexisting vessels. Initially, VEGF caused an accumulation of endothelial cells and macrophages, followed by networks of vascular channels and hemangiomas with locally high serum VEGF levels. No effects were evident in adjacent tissue or contralateral legs, where low serum VEGF was detected. These data suggest that the induction by VEGF of angiogenesis or vasculogenesis may be dose-dependent. Furthermore, VEGF expression must be carefully modulated, as overexpression is deleterious.
Springer
M L
ML
Department of Molecular Pharmacology, Stanford University School of Medicine, CA 94305-5332, USA.
Chen
A S
AS
Kraft
P E
PE
Bednarski
M
M
Blau
H M
HM
D000123:Acetyltransferases; D000818:Animals; D015153:Blotting, Western; D002465:Cell Movement; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000009:adverse effects / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology; D004797:Enzyme-Linked Immunosorbent Assay; D005121:Extremities / Q000098:blood supply*; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006391:Hemangioma / Q000098:blood supply; D051548:Histone Acetyltransferases; D008222:Lymphokines / Q000009:adverse effects / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D008264:Macrophages / Q000166:cytology; D008279:Magnetic Resonance Imaging; D051379:Mice; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D018919:Neovascularization, Physiologic; D012190:Retroviridae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D008222:Lymphokines; D029701:Saccharomyces cerevisiae Proteins; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D000123:Acetyltransferases; D051548:Histone Acetyltransferases