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

被引：32
作者：
Guo-Yuan Yang
Bin Xu
Tomoki Hashimoto
Madeleine Huey
Thomas Chaly
Rong Wen
William L. Young
机构：
[1] Department of Anesthesia, Center for Cerebrovascular Research, University of California, San Francisco, CA
[2] Department of Neurological Surgery, University of California, San Francisco, CA
[3] Department of Neurosurgery, University of California, San Francisco, CA
[4] Department of Neurosurgery, Hua-Shan Hospital, Fu-Dan University, Shanghai
[5] Department of Ophthalmology, School of Medicine, University of Pennsylvania, Philadelphia, PA
[6] Department of Anesthesia, University of California, Center for Cerebrovascular Research, San Francisco, CA 94110
来源：
Angiogenesis | 2003年 / 6卷 / 2期
基金：
美国国家卫生研究院;
关键词：
Adenoviral vector; Angiogenesis; Brain; Gene transfer; Microvasculature; Vascular endothelial growth factor;
D O I：
10.1023/B:AGEN.0000011803.56605.78
中图分类号：
学科分类号：
摘要：
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.
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页码：151 / 158
页数：7
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