title: Decrease in VEGF expression induces intussusceptive vascular pruning.
abstract: OBJECTIVE
  The concept of vascular pruning, the "cuting-off" of vessels, is gaining importance due to expansion of angio-modulating therapies. The proangiogenic effects of vascular endothelial growth factor (VEGF) are broadly described, but the mechanisms of structural alterations by its downregulation are not known.
  
  
  RESULTS
  VEGF(165)-releasing hydrogels were applied onto the chick chorioallantoic membrane on embryonic day 10. The hydrogels, designed to completely degrade within 2 days, caused high-level VEGF presentation followed by abrupt VEGF withdrawal. Application of VEGF resulted in a pronounced angiogenic response within 24 hours. The drastic decrease in level of exogenous VEGF-A within 48 hours was corroborated by enzyme-linked immunosorbent assay. Following this VEGF withdrawal we observed vasculature adaptation by means of intussusception, including intussusceptive vascular pruning. As revealed on vascular casts and serial semithin sections, intussusceptive vascular pruning occurred by emergence of multiple eccentric pillars at bifurcations. Time-lapse in vivo microscopy has confirmed the de novo occurrence of transluminal pillars and their capability to induce pruning. Quantitative evaluation corroborated an extensive activation of intussusception associated with VEGF withdrawal.
  
  
  CONCLUSIONS
  Diminution of VEGF level induces vascular tree regression by intussusceptive vascular pruning. This observation may allude to the mechanism underlying the "normalization" of tumor vasculature if treated with antiangiogenic drugs. The mechanism described here gives new insights into the understanding of the processes of vasculature regression and hence provides new and potentially viable targets for antiangiogenic and/or angio-modulating therapies during various pathological processes.
authors.affiliation: Institute of Anatomy, University of Fribourg, Fribourg, Switzerland.
authors.forename: Ruslan
authors.initials: R
authors.lastname: Hlushchuk
authors.forename: Martin
authors.initials: M
authors.lastname: Ehrbar
authors.forename: Philipp
authors.initials: P
authors.lastname: Reichmuth
authors.forename: Niklas
authors.initials: N
authors.lastname: Heinimann
authors.forename: Beata
authors.initials: B
authors.lastname: Styp-Rekowska
authors.forename: Robert
authors.initials: R
authors.lastname: Escher
authors.forename: Oliver
authors.initials: O
authors.lastname: Baum
authors.forename: Philipp
authors.initials: P
authors.lastname: Lienemann
authors.forename: Andrew
authors.initials: A
authors.lastname: Makanya
authors.forename: Eli
authors.initials: E
authors.lastname: Keshet
authors.forename: Valentin
authors.initials: V
authors.lastname: Djonov
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002642:Chick Embryo; D049033:Chorioallantoic Membrane / Q000098:blood supply*; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D023421:Models, Animal; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000172:deficiency* / Q000235:genetics / Q000494:pharmacology
chemical_list: D042461:Vascular Endothelial Growth Factor A