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An Engineered Heparin-Binding Form of VEGF-E (hbVEGF-E). Biological effects in vitro and mobilizatiion of precursor cells

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Abstract

Vascular endothelial growth factor (VEGF-A) is the founding member of a family of angiogenic proteins with various binding abilities to three cognate VEGF receptors. Previously, a gene encoding from the genome of parapox orf virus (OV) with about 25% amino acid identity to mammalian VEGF-A was named VEGF-E and shown to bind and specifically activate the vascular endothelial growth factor receptor VEGFR-2 (KDR/flk-1). Here, we have generated a novel heparin-binding form of VEGF-E by introducing the heparin-domain of the human VEGF-A165 splice variant into the viral VEGF-E protein. Recombinant heparin-binding VEGF-E (hbVEGF-E) is shown to stimulate proliferation and sprout formation of macro- and microvascular endothelial cells to a similar extent as the parental OV-VEGF-E but fails to activate peripheral mononuclear cells. However, hbVEGF-E is more potent in binding competition assays with primary human endothelial cells when compared to the OV-VEGF-E. This can be explained by our finding that binding of hbVEGF-E but not of parental OV-VEGF-E to the VEGFR-2 is strongly increased by the addition of neuropilin-1 (NP-1), a cognate co-receptor for VEGF-A. The engineered hbVEGF-E was compared with the VEGFR-1 selective and also heparin-binding form of placenta growth factor (PlGF-2)in vivo. Both heparin-binding homologues induced mobilization of endothelial progenitor cells from the bone marrow and gave rise to similar colony numbers of myeloic cells in a colony-forming assay. These findings suggest that both VEGFR-1 and VEGFR-2 are involved in stem cell mobilization.

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Author notes

  1. Matthias Clauss

    Present address: Department of Cellular and Integrative Physiology, Indiana Center for Vascular Biology & Medicine, Indianapolis, Indiana, USA

Authors and Affiliations

  1. Department of Experimental Cardiology, Molecular Cell Biology, Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany

    Matthias Heil, Katja Issbrücker & Wolfgang Schaper

  2. Molecular Cell Biology, Max-Planck-Institute for Physiological and Clinical Research, Bad Nauheim, Germany

    Rita Mitnacht-Krauss

  3. Biochemical Engineering, National Research Centre for Biotechnology (GBF), Braunschweig, Germany

    Joop van den Heuvel

  4. Biozentrum of University Basel, Basel, Switzerland

    Christoph Dehio

  5. Molecular Biotechnology, National Research Centre for Biotechnology (GBF), Braunschweig, Germany

    Herbert A. Weich

Authors
  1. Matthias Heil
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  2. Rita Mitnacht-Krauss
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  3. Katja Issbrücker
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  4. Joop van den Heuvel
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  5. Christoph Dehio
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  6. Wolfgang Schaper
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  7. Matthias Clauss
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  8. Herbert A. Weich
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Correspondence to Herbert A. Weich.

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Heil, M., Mitnacht-Krauss, R., Issbrücker, K. et al. An Engineered Heparin-Binding Form of VEGF-E (hbVEGF-E). Biological effects in vitro and mobilizatiion of precursor cells . Angiogenesis 6, 201–211 (2003). https://doi.org/10.1023/B:AGEN.0000021391.88601.92

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  • DOI: https://doi.org/10.1023/B:AGEN.0000021391.88601.92

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