01875nas a2200217   4500008004100000245015700041210006900198260001400267300001300281490000800294520113500302100002101437700002001458700002301478700002001501700002101521700002301542700002501565700001801590856004901608       2007                        eng d00aEnhanced capillary formation stimulated by a chimeric vascular endothelial growth factor/vascular endothelial growth factor-C silk domain fusion protein0 aEnhanced capillary formation stimulated by a chimeric vascular e  c2007/May/  a1460 - 70 v1003 aVascular endothelial growth factor (VEGF)-C and VEGF-D require proteolytic cleavage of the carboxy terminal silk-homology domain for activation. To study the functions of the VEGF-C propeptides, we engineered a chimeric growth factor protein, VEGF-CAC, composed of the amino- and carboxy-terminal propeptides of VEGF-C fused to the receptor-activating core domain of VEGF. Like VEGF-C, VEGF-CAC underwent proteolytic cleavage, and like VEGF, it bound to and activated VEGF receptor-1 and VEGF receptor-2, but not the VEGF-C receptor VEGF receptor-3. VEGF-CAC also bound to neuropilins in a heparin-dependent manner. Strikingly, when VEGF-CAC was expressed via an adenovirus vector in the ear skin of immunodeficient mice, it proved to be a more potent inducer of capillary angiogenesis than VEGF. The VEGF-CAC-induced vessels differed greatly from those induced by VEGF, as they formed a very dense and fine network of pericyte and basement membrane-covered capillaries that were functional, as shown by lectin perfusion experiments. VEGF-CAC could prove useful in proangiogenic therapies in patients experiencing tissue ischemia.1 aKeskitalo, Salla1 aTammela, Tuomas1 aLyytikka, Johannes1 aKarpanen, Terhi1 aJeltsch, Michael1 aMarkkanen, Johanna1 aYla-Herttuala, Seppo1 aAlitalo, Kari  uhttp://view.ncbi.nlm.nih.gov/pubmed/17478734