Angiogenic synergy of bFGF and VEGF is antagonized by Angiopoietin-2 in a modified in vivo Matrigel assay
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Angiogenic synergy of bFGF and VEGF is antagonized by Angiopoietin-2 in a modified in vivo Matrigel assay. / Ley, Carsten D.; Olsen, Minna W.B.; Lund, Eva L.; Kristjansen, Paul E.G.
In: Microvascular Research, Vol. 68, No. 3, 11.2004, p. 161-168.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Angiogenic synergy of bFGF and VEGF is antagonized by Angiopoietin-2 in a modified in vivo Matrigel assay
AU - Ley, Carsten D.
AU - Olsen, Minna W.B.
AU - Lund, Eva L.
AU - Kristjansen, Paul E.G.
N1 - Funding Information: This research was supported by grants from the Danish Cancer Society and the Danish Medical Research Council. Furthermore, we would like to thank our laboratory technicians Karen Juhl and Pia G. Knudsen for their valuable assistance.
PY - 2004/11
Y1 - 2004/11
N2 - A murine modification of the Matrigel chamber assay originally developed for use on rats is presented. This modified assay permits improved quantification due to subcutaneous Matrigel implants of constant shape and volume. We have quantitatively assessed the angiogenic potential of the growth factors basic fibroblast growth factor (bFGF), VEGF, and Angiopoietin-2 (Ang-2) with special emphasis on their mutual interactions. A reproducible dose-response relationship for bFGF was established for doses between 150 and 1000 ng per chamber, whereas VEGF did not display angiogenic activity on its own in the tested dose of up to 200 ng per chamber. Conversely, we found a strong synergistic action of bFGF and VEGF when combined in a 3:1 ratio. Two other combinations (ratios) with greater VEGF doses were also tested, but the synergistic effect was only observed when 50 ng of VEGF was added to 150 ng per chamber of bFGF. This synergistic effect of bFGF and VEGF was significantly reduced by further addition of 100 ng Angiopoietin-2. Inhibition of the response to bFGF and VEGF was confirmed by in vitro EC migration experiments, which, together with our in vivo results, indicates that Ang-2 may target chemotactic responses to bFGF and VEGF in vivo.
AB - A murine modification of the Matrigel chamber assay originally developed for use on rats is presented. This modified assay permits improved quantification due to subcutaneous Matrigel implants of constant shape and volume. We have quantitatively assessed the angiogenic potential of the growth factors basic fibroblast growth factor (bFGF), VEGF, and Angiopoietin-2 (Ang-2) with special emphasis on their mutual interactions. A reproducible dose-response relationship for bFGF was established for doses between 150 and 1000 ng per chamber, whereas VEGF did not display angiogenic activity on its own in the tested dose of up to 200 ng per chamber. Conversely, we found a strong synergistic action of bFGF and VEGF when combined in a 3:1 ratio. Two other combinations (ratios) with greater VEGF doses were also tested, but the synergistic effect was only observed when 50 ng of VEGF was added to 150 ng per chamber of bFGF. This synergistic effect of bFGF and VEGF was significantly reduced by further addition of 100 ng Angiopoietin-2. Inhibition of the response to bFGF and VEGF was confirmed by in vitro EC migration experiments, which, together with our in vivo results, indicates that Ang-2 may target chemotactic responses to bFGF and VEGF in vivo.
KW - Ang-2
KW - Angiogenesis
KW - bFGF
KW - Matrigel
KW - Migration
KW - Synergy
KW - VEGF
UR - http://www.scopus.com/inward/record.url?scp=14244263841&partnerID=8YFLogxK
U2 - 10.1016/j.mvr.2004.06.002
DO - 10.1016/j.mvr.2004.06.002
M3 - Journal article
C2 - 15501235
AN - SCOPUS:14244263841
VL - 68
SP - 161
EP - 168
JO - Microvascular Research
JF - Microvascular Research
SN - 0026-2862
IS - 3
ER -
ID: 288186298