title: Radiation attenuates physiological angiogenesis by differential expression of VEGF, Ang-1, tie-2 and Ang-2 in rat brain.
abstract: The etiology of radiation-induced cerebrovascular rarefaction remains unknown. In the present study, we examined the effect of whole-brain irradiation on endothelial cell (EC) proliferation/apoptosis and expression of various angiogenic factors in rat brain. F344 × BN rats received either whole-brain irradiation (a single dose of 10 Gy γ rays) or sham irradiation and were maintained for 4, 8 and 24 h after irradiation. Double immunofluorescence staining was employed to visualize EC proliferation/apoptosis in brain. The mRNA and protein expression levels of vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1), endothelial-specific receptor tyrosine kinase (Tie-2), and Ang-2 in brain were determined by real-time RT-PCR and immunofluorescence staining. A significant reduction in CD31-immunoreactive cells was detected in irradiated rat brains compared with sham-irradiated controls. Whole-brain irradiation significantly suppressed EC proliferation and increased EC apoptosis. In addition, a significant decrease in mRNA and protein expression of VEGF, Ang-1 and Tie-2 was observed in irradiated rat brains. In contrast, whole-brain irradiation significantly upregulated Ang-2 expression in rat brains. The present study provides novel evidence that whole-brain irradiation differentially affects mRNA and protein expression of VEGF, Ang-1, Tie-2 and Ang-2. These changes are closely associated with decreased EC proliferation and increased EC apoptosis in brain.
authors.affiliation: School of Biomedical Engineering and Sciences, Virginia Tech, Blacksburg, Virginia 24061, USA.
authors.forename: Won Hee
authors.initials: WH
authors.lastname: Lee
authors.forename: Hyung Joon
authors.initials: HJ
authors.lastname: Cho
authors.forename: William E
authors.initials: WE
authors.lastname: Sonntag
authors.forename: Yong Woo
authors.initials: YW
authors.lastname: Lee
mesh_terms: D042683:Angiopoietin-1 / Q000235:genetics*; D042702:Angiopoietin-2 / Q000235:genetics*; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D001921:Brain / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects*; D049109:Cell Proliferation / Q000528:radiation effects; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects*; D008297:Male; D018919:Neovascularization, Physiologic / Q000528:radiation effects*; D051381:Rats; D042787:Receptor, TIE-2 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D042683:Angiopoietin-1; D042702:Angiopoietin-2; D042461:Vascular Endothelial Growth Factor A; D042787:Receptor, TIE-2