How Is the Formation of Branching Points at the Molecular Level Regulated?
The currently known pro-angiogenic molecules have been characterized by their effect on endothelial cell proliferation, migration and tube formation. The most prominent ones of these growth factors are fibroblast growth factor 1 and 2 (FGF-1, acidic and FGF-2, basic), platelet-derived growth factor (PDGF), hepatocyte growth factor (HGF, scatter factor), vascular endothelial growth factor/vascular permeability factor (VEGF-A, VEGF-B, VEGF-C), transforming growth factor alpha (TGF-α), and interleukin 8 (IL-8).41-44 Additionally, an important role in angiogenesis has been established for the Tie/Angiopoietin and the Eph-B/ephrin-B system of tyrosine kinase receptors and their ligands.23>,33>,45-50 It has been shown that the heparin-binding isoform of VEGF-A is especially responsible for vascular branching. Transgenic mice that solely expressed the VEGF-A isoform, which lacks heparin binding (VEGF 120/120), exhibited larger vessels with more endothelial cells, but fewer vessel branches as
