The mouse aorta model: influence of genetic background and aging on bFGF- and VEGF-induced angiogenic sprouting.
Angiogenesis can be studied ex vivo by culturing rat or mouse aortic rings in collagen gels. Unlike rat aorta explants, unstimulated mouse aortic rings were unable to spontaneously produce an angiogenic response under serum-free conditions. They, however, responded to bFGF and VEGF, generating networks of branching neovessels. Aortic rings from GFP-Tie2-transgenic mice generated GFP-labeled neovessels that could be easily identified by their distinctly green fluorescence. Aortic rings from 1- to 2-month-old mice produced microvessels faster, more uniformly and in greater number than aortic rings from 6- to 10-month-old mice, particularly in VEGF-treated cultures. Aortic rings from 129/SVJ mice were capable of a much stronger and sustained angiogenic response to bFGF than those of C57BL/6 or BALB/c mice, which were in turn more angiogenic than aortic rings from FVB mice. The same strains of mice responded differently to VEGF, as C57BL/6 mouse aortic rings produced more microvessels than those of BALB/c, FVB, and 129/SVJ mice, which were capable of only a limited response. The significant impact that aging and genetic background have on mouse aortic angiogenesis should be taken into account when the aortic-ring assay is used to evaluate function of genes that have been deleted or overexpressed in genetically modified mice.
Zhu
Wen-Hui
WH
Department of Pathology, University of Washington, Seattle, Washington, USA.
Iurlaro
Monica
M
MacIntyre
Angela
A
Fogel
Eric
E
Nicosia
Roberto F
RF
D000367:Age Factors; D000818:Animals; D001011:Aorta / Q000502:physiology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D066298:In Vitro Techniques; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D042787:Receptor, TIE-2 / Q000235:genetics; D013045:Species Specificity; D019076:Transgenes / Q000502:physiology*; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D042787:Receptor, TIE-2