Functional Overlap Between Chondroitin and Heparan Sulfate Proteoglycans During VEGF-Induced Sprouting Angiogenesis
2012 (English)In: Arteriosclerosis, Thrombosis and Vascular Biology, ISSN 1079-5642, E-ISSN 1524-4636, Vol. 32, no 5, 1255-1263 p.Article in journal (Refereed) Published
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.
METHODS AND 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, TGFβ, 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 TGFβ 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.
Place, publisher, year, edition, pages
2012. Vol. 32, no 5, 1255-1263 p.
Angiogenesis, proteoglycan, heparan sulfate, chondroitin sulfate, ext1
Research subject Medicine; Biology with specialization in Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-169136DOI: 10.1161/ATVBAHA.111.240622ISI: 000303195100031PubMedID: 22345168OAI: oai:DiVA.org:uu-169136DiVA: diva2:505091
FunderSwedish Research Council, K2011-67X-21868-01-3