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Functional overlap between chondroitin and heparan sulfate proteoglycans during VEGF-induced sprouting angiogenesis.
Le Jan, Sébastien; Hayashi, Makoto; Kasza, Zsolt; Eriksson, Inger; Bishop, Joseph R; Weibrecht, Irene; Heldin, Johan; Holmborn, Katarina; Jakobsson, Lars; Söderberg, Ola; Spillmann, Dorothe; Esko, Jeffrey D; Claesson-Welsh, Lena; Kjellén, Lena; Kreuger, Johan.
Afiliação
  • Le Jan S; Rudbeck Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
Arterioscler Thromb Vasc Biol ; 32(5): 1255-63, 2012 May.
Article em En | MEDLINE | ID: mdl-22345168
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, transforming growth factor ß, 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 ß 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.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoglicanas / Endotélio Vascular / Proteoglicanas de Heparan Sulfato / Fator A de Crescimento do Endotélio Vascular / Neovascularização Patológica Limite: Animals Idioma: En Ano de publicação: 2012 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteoglicanas / Endotélio Vascular / Proteoglicanas de Heparan Sulfato / Fator A de Crescimento do Endotélio Vascular / Neovascularização Patológica Limite: Animals Idioma: En Ano de publicação: 2012 Tipo de documento: Article