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Article: Glycosaminoglycan regulation by VEGFA and VEGFC of the glomerular microvascular endothelial cell glycocalyx in vitro

TitleGlycosaminoglycan regulation by VEGFA and VEGFC of the glomerular microvascular endothelial cell glycocalyx in vitro
Authors
Issue Date2013
Citation
American Journal of Pathology, 2013, v. 183 n. 2, p. 604-616 How to Cite?
AbstractDamage to endothelial glycocalyx impairs vascular barrier function and may contribute to progression of chronic vascular disease. An early indicator is microalbuminuria resulting from glomerular filtration barrier damage. We investigated the contributions of hyaluronic acid (HA) and chondroitin sulfate (CS) to glomerular microvascular endothelial cell (GEnC) glycocalyx and examined whether these are modified by vascular endothelial growth factors A and C (VEGFA and VEGFC). HA and CS were imaged on GEnCs and their resynthesis was examined. The effect of HA and CS on transendothelial electrical resistance (TEER) and labeled albumin flux across monolayers was assessed. Effects of VEGFA and VEGFC on production and charge characteristics of glycosaminoglycan (GAG) were examined via metabolic labeling and liquid chromatography. GAG shedding was quantified using Alcian Blue. NDST2 expression was examined using real-time PCR. GEnCs expressed HA and CS in the glycocalyx. CS contributed to the barrier to both ion (TEER) and protein flux across the monolayer; HA had only a limited effect. VEGFC promoted HA synthesis and increased the charge density of synthesized GAGs. In contrast, VEGFA induced shedding of charged GAGs. CS plays a role in restriction of macromolecular flux across GEnC monolayers, and VEGFA and VEGFC differentially regulate synthesis, charge, and shedding of GAGs in GEnCs. These observations have important implications for endothelial barrier regulation in glomerular and other microvascular beds. © 2013 American Society for Investigative Pathology.
Persistent Identifierhttp://hdl.handle.net/10722/195409
ISSN
2015 Impact Factor: 4.206
2015 SCImago Journal Rankings: 2.653
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFoster, RR-
dc.contributor.authorArmstrong, L-
dc.contributor.authorBaker, S-
dc.contributor.authorWong, DWL-
dc.contributor.authorWylie, EC-
dc.contributor.authorRamnath, R-
dc.contributor.authorJenkins, R-
dc.contributor.authorSingh, A-
dc.contributor.authorSteadman, R-
dc.contributor.authorWelsh, GI-
dc.contributor.authorMathieson, PW-
dc.contributor.authorSatchell, SC-
dc.date.accessioned2014-02-28T06:12:06Z-
dc.date.available2014-02-28T06:12:06Z-
dc.date.issued2013-
dc.identifier.citationAmerican Journal of Pathology, 2013, v. 183 n. 2, p. 604-616-
dc.identifier.issn0002-9440-
dc.identifier.urihttp://hdl.handle.net/10722/195409-
dc.description.abstractDamage to endothelial glycocalyx impairs vascular barrier function and may contribute to progression of chronic vascular disease. An early indicator is microalbuminuria resulting from glomerular filtration barrier damage. We investigated the contributions of hyaluronic acid (HA) and chondroitin sulfate (CS) to glomerular microvascular endothelial cell (GEnC) glycocalyx and examined whether these are modified by vascular endothelial growth factors A and C (VEGFA and VEGFC). HA and CS were imaged on GEnCs and their resynthesis was examined. The effect of HA and CS on transendothelial electrical resistance (TEER) and labeled albumin flux across monolayers was assessed. Effects of VEGFA and VEGFC on production and charge characteristics of glycosaminoglycan (GAG) were examined via metabolic labeling and liquid chromatography. GAG shedding was quantified using Alcian Blue. NDST2 expression was examined using real-time PCR. GEnCs expressed HA and CS in the glycocalyx. CS contributed to the barrier to both ion (TEER) and protein flux across the monolayer; HA had only a limited effect. VEGFC promoted HA synthesis and increased the charge density of synthesized GAGs. In contrast, VEGFA induced shedding of charged GAGs. CS plays a role in restriction of macromolecular flux across GEnC monolayers, and VEGFA and VEGFC differentially regulate synthesis, charge, and shedding of GAGs in GEnCs. These observations have important implications for endothelial barrier regulation in glomerular and other microvascular beds. © 2013 American Society for Investigative Pathology.-
dc.languageeng-
dc.relation.ispartofAmerican Journal of Pathology-
dc.titleGlycosaminoglycan regulation by VEGFA and VEGFC of the glomerular microvascular endothelial cell glycocalyx in vitro-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.ajpath.2013.04.019-
dc.identifier.pmid23770346-
dc.identifier.scopuseid_2-s2.0-84880639927-
dc.identifier.volume183-
dc.identifier.issue2-
dc.identifier.spage604-
dc.identifier.epage616-
dc.identifier.isiWOS:000322611700027-

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