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 Citations (Scopus)

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

Fingerprint

Gene transfer
Endothelial cells
Cell growth
Vascular Endothelial Growth Factor A
Brain
Intercellular Signaling Peptides and Proteins
Genes
Microvessels
Proliferating Cell Nuclear Antigen
Mitogens
Tumors
Suspensions
Complementary DNA
Cells
Tissue
Injections
Ischemia
Endothelial Cells
Staining and Labeling

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

Cite this

Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain. / Yang, Guo Yuan; Xu, Bin; Hashimoto, Tomoki; Huey, Madeleine; Chaly, Thomas; Wen, Rong; Young, William L.

In: Angiogenesis, Vol. 6, No. 2, 01.12.2003, p. 151-158.

Research output: Contribution to journalArticle

Yang, Guo Yuan ; Xu, Bin ; Hashimoto, Tomoki ; Huey, Madeleine ; Chaly, Thomas ; Wen, Rong ; Young, William L. / Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain. In: Angiogenesis. 2003 ; Vol. 6, No. 2. pp. 151-158.
@article{8b86a55cb6f5465cbcf355b5072a7db5,
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 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.",
keywords = "Adenoviral vector, Angiogenesis, Brain, Gene transfer, Microvasculature, Vascular endothelial growth factor",
author = "Yang, {Guo Yuan} and Bin Xu and Tomoki Hashimoto and Madeleine Huey and Thomas Chaly and Rong Wen and Young, {William L.}",
year = "2003",
month = "12",
day = "1",
doi = "10.1023/B:AGEN.0000011803.56605.78",
language = "English",
volume = "6",
pages = "151--158",
journal = "Angiogenesis",
issn = "0969-6970",
publisher = "Springer Netherlands",
number = "2",

}

TY - JOUR

T1 - Induction of focal angiogenesis through adenoviral vector mediated vascular endothelial cell growth factor gene transfer in the mature mouse brain

AU - Yang, Guo Yuan

AU - Xu, Bin

AU - Hashimoto, Tomoki

AU - Huey, Madeleine

AU - Chaly, Thomas

AU - Wen, Rong

AU - Young, William L.

PY - 2003/12/1

Y1 - 2003/12/1

N2 - 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.

AB - 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.

KW - Adenoviral vector

KW - Angiogenesis

KW - Brain

KW - Gene transfer

KW - Microvasculature

KW - Vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=0842268487&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0842268487&partnerID=8YFLogxK

U2 - 10.1023/B:AGEN.0000011803.56605.78

DO - 10.1023/B:AGEN.0000011803.56605.78

M3 - Article

C2 - 14739621

AN - SCOPUS:0842268487

VL - 6

SP - 151

EP - 158

JO - Angiogenesis

JF - Angiogenesis

SN - 0969-6970

IS - 2

ER -