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Differential regulation of angiogenic factors by radiation in rat brain
Author(s) -
Lee Won Hee,
Sonntag William E.,
Lee Yong Woo
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.746.2
Subject(s) - angiopoietin receptor , hippocampal formation , angiopoietin , endocrinology , receptor , medicine , angiogenesis , vascular endothelial growth factor , irradiation , chemistry , biology , vegf receptors , physics , nuclear physics
It has been hypothesized that radiation‐induced brain injury is a consequence of rarefaction of cerebral microvasculature. In the present study, we investigated the molecular regulatory mechanisms of radiation‐induced vessel rarefaction in the brain. Four month old F344×BN rats received either whole brain irradiation with a single dose of 10 Gy γ‐rays or sham‐irradiation, and were maintained for 4, 8, and 24 h following irradiation. The expression levels of a variety of angiogenic factors such as angiopoietin‐1 (Ang‐1), angiopoietin‐2 (Ang‐2), endothelial receptor tyrosine kinase (Tie‐2), and vascular endothelial growth factor (VEGF) were analyzed by quantitative real‐time RT‐PCR. A significant down‐regulation of Ang‐1 and Tie‐2 was observed in hippocampal and cortical regions isolated from irradiated animals. In addition, irradiation significantly attenuated the mRNA and protein expression levels of VEGF. In contrast, Ang‐2 expression was significantly and dramatically up‐regulated in the irradiated brain, demonstrating that irradiation markedly reduces the ratio of Ang‐1/Ang‐2 and increases the ratio of Ang‐2/VEGF. These data provide the first evidence that vascular plasticity may be impaired in irradiated animals though differential regulation of Ang‐1, Tie‐2, Ang‐2 and VEGF in the brain, and this may contribute to cerebrovascular rarefaction. (This work was supported by NINDS R01NS056218)