title: Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain.
abstract: Vascular endothelial growth factor (VEGF) is a potent endothelial cell mitogen and morphogen, which stimulates angiogenesis in a wide variety of tissues and lesions in vivo. In this study, we applied adenoviral vector delivered human VEGF165 cDNA to develop focal non-tumor angiogenesis in the mature mouse brain. Seventy-two adult CD-1 mice underwent Ad h VEGF, Ad lacZ, and saline injection for up to fourweeks. An adenoviral suspension containing 1 x 10(9) particles was injected stereotactically into the right hemisphere of the brain. The results showed that VEGF expression was increased in the Ad h VEGF transduced mice compared to Ad lacZ or saline injected mice ( P < 0.05). VEGF-positive cells were mainly located in the injection hemisphere of Ad h VEGF transduced mice. Quantitative vessel counting showed that microvessels in the Ad h VEGF transduced mice increased following 2 weeks of Ad h VEGF gene transfer compared to the other two groups (Ad h VEGF:241 +/- 19 vs. Ad lacZ :148 +/- 17 and Saline:150 +/- 14 vessels/mm2, P < 0.05). Morphology showed typical angiogenic changes. PCNA-positive staining confirmed these microvessels were actively proliferating. Our study demonstrates that Ad h VEGF-induced VEGF hyper-stimulation causes focal angiogenesis in the mature mouse brain. This novel method of inducing in vivo brain focal angiogenesis provides an opportunity to study the molecular mechanisms independent of the confounding effects of upstream inciting stimuli such as ischemia or tumor.
authors.affiliation: Departments of Anesthesia and Neurosurgery, The Center for Cerebrovascular Research, University of California, San Francisco, California, USA. gyyang@anesthesia.ucsf.edu
authors.forename: Guo-Yuan
authors.initials: GY
authors.lastname: Yang
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Tomoki
authors.initials: T
authors.lastname: Hashimoto
authors.forename: Madeleine
authors.initials: M
authors.lastname: Huey
authors.forename: Thomas
authors.initials: T
authors.lastname: Chaly
authors.forename: Rong
authors.initials: R
authors.lastname: Wen
authors.forename: William L
authors.initials: WL
authors.lastname: Young
mesh_terms: D000256:Adenoviridae; D000818:Animals; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D017930:Genes, Reporter; D005822:Genetic Vectors; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D018919:Neovascularization, Physiologic / Q000235:genetics*; D014161:Transduction, Genetic; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: D042461:Vascular Endothelial Growth Factor A