1. Synthesis and physiological activity of heterodimers comprising different splice forms of vascular endothelial growth factor and placenta growth factor
- Author
-
John E.G. McCarthy, Ralf Birkenhäger, Bernard Schneppe, Jörg Wilting, Herbert A. Weich, and Wolfgang Röckl
- Subjects
Vascular Endothelial Growth Factor A ,Angiogenesis ,Placenta ,Recombinant Fusion Proteins ,Restriction Mapping ,Neovascularization, Physiologic ,Chick Embryo ,Endothelial Growth Factors ,Pregnancy Proteins ,Biology ,Biochemistry ,chemistry.chemical_compound ,Pregnancy ,In vivo ,Escherichia coli ,Animals ,Humans ,Cloning, Molecular ,Molecular Biology ,Cells, Cultured ,Placenta Growth Factor ,Lymphokines ,DNA synthesis ,Vascular Endothelial Growth Factors ,Microcirculation ,Cell Biology ,Molecular biology ,Cell biology ,Vascular endothelial growth factor B ,Vascular endothelial growth factor ,Alternative Splicing ,Vascular endothelial growth factor A ,Vascular endothelial growth factor C ,chemistry ,PIGF ,Angiogenesis Inducing Agents ,Female ,Endothelium, Vascular ,Cell Division ,Research Article - Abstract
Vascular endothilial growth factor (VEGF) and placenta growth factor (PIGF) are members of a dimeric-growth-factor family with angiogenic properties. VEGF is a highly potent and specific mitogen for endothelial cells, playing a vital role in angiogenesis in vivo. The role of PIGF is less clear. We expressed the monomeric splice forms VEGF-165, VEGF-121, PIGF-1 and PlGF-2 as unfused genes in Escherichia coli using the pCYTEXP expression system. In vitro dimerization experiments revealed that both homo- and hetero-dimers can be formed from these monomeric proteins. The dimers were tested for their ability to promote capillary growth in vivo and stimulate DNA synthesis in cultured human vascular endothelial cells. Heterodimers comprising different VEGF splice forms, or combinations of VEGF/PlGF splice forms, showed mitogenic activity. The results demonstrate that four different heterodimeric growth factors are likely to have as yet uncharacterized functions in vivo.
- Published
- 1996