Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain

Guo Yuan Yang, Bin Xu, Tomoki Hashimoto, Madeleine Huey, Thomas Chaly, Rong Wen, William L. Young

Research output: Contribution to journalArticle

34 Scopus citations

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 AdhVEGF, AdlacZ, and saline injection for up to four weeks. An adenoviral suspension containing 1 × 109 particles was injected stereotactically into the right hemisphere of the brain. The results showed that VEGF expression was increased in the AdhVEGF transduced mice compared to AdlacZ or saline injected mice (P < 0.05). VEGF-positive cells were mainly located in the injection hemisphere of AdhVEGF transduced mice. Quantitative vessel counting showed that microvessels in the AdhVEGF transduced mice increased following 2 weeks of AdhVEGF gene transfer compared to the other two groups (AdhVEGF:241 ± 19 vs. AdlacZ: 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 AdhVEGF-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.

Original languageEnglish (US)
Pages (from-to)151-158
Number of pages8
JournalAngiogenesis
Volume6
Issue number2
DOIs
StatePublished - Dec 1 2003
Externally publishedYes

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Keywords

  • Adenoviral vector
  • Angiogenesis
  • Brain
  • Gene transfer
  • Microvasculature
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Cancer Research
  • Pathology and Forensic Medicine
  • Clinical Biochemistry
  • Polymers and Plastics

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