title: Functional overlap between chondroitin and heparan sulfate proteoglycans during VEGF-induced sprouting angiogenesis.
abstract: OBJECTIVE
  Heparan sulfate proteoglycans regulate key steps of blood vessel formation. The present study was undertaken to investigate if there is a functional overlap between heparan sulfate proteoglycans and chondroitin sulfate proteoglycans during sprouting angiogenesis.
  
  
  RESULTS
  Using cultures of genetically engineered mouse embryonic stem cells, we show that angiogenic sprouting occurs also in the absence of heparan sulfate biosynthesis. Cells unable to produce heparan sulfate instead increase their production of chondroitin sulfate that binds key angiogenic growth factors such as vascular endothelial growth factor A, transforming growth factor β, and platelet-derived growth factor B. Lack of heparan sulfate proteoglycan production however leads to increased pericyte numbers and reduced adhesion of pericytes to nascent sprouts, likely due to dysregulation of transforming growth factor β and platelet-derived growth factor B signal transduction.
  
  
  CONCLUSIONS
  The present study provides direct evidence for a previously undefined functional overlap between chondroitin sulfate proteoglycans and heparan sulfate proteoglycans during sprouting angiogenesis. Our findings provide information relevant for potential future drug design efforts that involve targeting of proteoglycans in the vasculature.
authors.affiliation: Rudbeck Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Le Jan
authors.forename: Makoto
authors.initials: M
authors.lastname: Hayashi
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Kasza
authors.forename: Inger
authors.initials: I
authors.lastname: Eriksson
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Bishop
authors.forename: Irene
authors.initials: I
authors.lastname: Weibrecht
authors.forename: Johan
authors.initials: J
authors.lastname: Heldin
authors.forename: Katarina
authors.initials: K
authors.lastname: Holmborn
authors.forename: Lars
authors.initials: L
authors.lastname: Jakobsson
authors.forename: Ola
authors.initials: O
authors.lastname: Söderberg
authors.forename: Dorothe
authors.initials: D
authors.lastname: Spillmann
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Esko
authors.forename: Lena
authors.initials: L
authors.lastname: Claesson-Welsh
authors.forename: Lena
authors.initials: L
authors.lastname: Kjellén
authors.forename: Johan
authors.initials: J
authors.lastname: Kreuger
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D002807:Chondroitin; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D019812:Heparan Sulfate Proteoglycans / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D009389:Neovascularization, Pathologic / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011509:Proteoglycans / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
chemical_list: D019812:Heparan Sulfate Proteoglycans; D011509:Proteoglycans; D042461:Vascular Endothelial Growth Factor A; D002807:Chondroitin