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Transgenic Overexpression of Vascular Endothelial Growth
Factor-B Isoforms by Endothelial Cells Potentiates
Postnatal Vessel Growth In Vivo and In Vitro
by Arne W. Mould, Sonia A. Greco, Marian M. Cahill, Ian D. Tonks, Daniela Bellomo,
Carol Patterson, Anna Zournazi, Andrew Nash, Pierre Scotney, Nicholas K. Hayward,
and Graham F. Kay
Circulation Research
Volume 97(6):e60-e70
September 16, 2005
Copyright © American Heart Association, Inc. All rights reserved.
Figure 1. Transgenic VEGFB167 and VEGFB186 expression constructs and analysis of transgene
expression in VEGFB186Tg and VEGFB167Tg mice. a, The cDNA and SV40 poly A signal
sequence of either VEGFB167 or VEGFB186 were inserted between the Tie2 promoter and
enhancer regions.
Arne W. Mould et al. Circ Res. 2005;97:e60-e70
Copyright © American Heart Association, Inc. All rights reserved.
Figure 2. The functional analysis of recombinant human and mouse VEGF-B and anti–VEGF-B
mAb. a, Human and mouse VEGF-B amino acid isoforms (residues 10 to 108 and 1 to 167)
expressed in E coli were purified and refolded, then analyzed by SDS-PAGE (10% to 20%
gradient) under nonreducing and reducing conditions.
Arne W. Mould et al. Circ Res. 2005;97:e60-e70
Copyright © American Heart Association, Inc. All rights reserved.
Figure 3. VEGFB167Tg and VEGFB186Tg mice display increased vessel density in the Matrigel
plug assay and in healing cutaneous wounds. a, Photomicrograph of a cryosection (7 μm) from
a Matrigel plug harvested after 6 days in vivo showing vessel in growth, as assessed by PECAM1 immunolabeling of endothelial cells.
Arne W. Mould et al. Circ Res. 2005;97:e60-e70
Copyright © American Heart Association, Inc. All rights reserved.
Figure 4. The levels of EPCs in the blood of VEGFB167Tg and VEGFB186Tg mice.
Arne W. Mould et al. Circ Res. 2005;97:e60-e70
Copyright © American Heart Association, Inc. All rights reserved.
Figure 5. Increased vessel sprouting in aortic explants from VEGFB186Tg and VEGFB167Tg
mice. a, Black and white photomicrograph of a 6-day-old wild-type aortic explant culture stained
with FITC-BS-1 lectin, showing vessel-like endothelial outgrowth from explant into the
surrounding collagen gel.
Arne W. Mould et al. Circ Res. 2005;97:e60-e70
Copyright © American Heart Association, Inc. All rights reserved.
Figure 6. VEGF-B does not induce vascular leakage in the Miles assay.
Arne W. Mould et al. Circ Res. 2005;97:e60-e70
Copyright © American Heart Association, Inc. All rights reserved.