Vascular endothelial growth factor increases endothelial cell permeability in vitro

Research output: Contribution to journalArticle

Abstract

Purpose. Vascular endothelial growth factor (VEGF) is upregulated in retinal glia during hypoxia, but it is constitutively expressed only by the pigment epithelium in healthy adult retinas. VEGF increases vessel permeability to plasma proteins in vivo. Thus, it may have a role in inducing and maintaining the enhanced permeability of the choriocapillaris endothelium which abuts the pigment epithelium. Methods. We tested this hypothesis and analyzed mechanisms of VEGF-induced permeability alterations using early passage cultures of bovine retinal microvascular endothelial cells and bioassays for permeability, transcellular electrical resistance (TER), and morphology. Results. VEGF treatment induced a rapid and statistically significant increase in permeability to horseradish peroxidase (HRP, 40 kDa) and socium fluorescein (SF, 0.4 KDa). The rate of increase in HRP permeability (66%) was three times that of SF (22%). TER was not affected. Gross morphology of the treated cultures was not altered as indicated by actin localization or scanning electron microscopy. High resolution analysis suggested that the vesicles/fenestrations of the VEGF-treated cells were larger and more abundant as compared with controls. Conclusions. VEGF induces an increase in endothelial cell permeability The large HRP protein is thought to cross primarily via vesicles and fenestrations, whereas the small SF molecule crosses by both paracellular and transcellular routes. Taken with the lack of change in TER and apparent increase in vesicles/fenestrations, these data suggest that VEGF acts by altering transcellular permeability through fenestrations and vesicles.

Original languageEnglish (US)
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

Fingerprint

Vascular Endothelial Growth Factor A
Permeability
Endothelial Cells
Electric Impedance
Epithelium
In Vitro Techniques
Horseradish Peroxidase
Fluorescein
Neuroglia
Biological Assay
Electron Scanning Microscopy
Endothelium
Retina
Actins
Blood Proteins
Proteins

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Vascular endothelial growth factor increases endothelial cell permeability in vitro. / Caldwell, Ruth B; Feng, Y.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996.

Research output: Contribution to journalArticle

@article{c70bb5ab2df14791bfb011409d8ffcb8,
title = "Vascular endothelial growth factor increases endothelial cell permeability in vitro",
abstract = "Purpose. Vascular endothelial growth factor (VEGF) is upregulated in retinal glia during hypoxia, but it is constitutively expressed only by the pigment epithelium in healthy adult retinas. VEGF increases vessel permeability to plasma proteins in vivo. Thus, it may have a role in inducing and maintaining the enhanced permeability of the choriocapillaris endothelium which abuts the pigment epithelium. Methods. We tested this hypothesis and analyzed mechanisms of VEGF-induced permeability alterations using early passage cultures of bovine retinal microvascular endothelial cells and bioassays for permeability, transcellular electrical resistance (TER), and morphology. Results. VEGF treatment induced a rapid and statistically significant increase in permeability to horseradish peroxidase (HRP, 40 kDa) and socium fluorescein (SF, 0.4 KDa). The rate of increase in HRP permeability (66{\%}) was three times that of SF (22{\%}). TER was not affected. Gross morphology of the treated cultures was not altered as indicated by actin localization or scanning electron microscopy. High resolution analysis suggested that the vesicles/fenestrations of the VEGF-treated cells were larger and more abundant as compared with controls. Conclusions. VEGF induces an increase in endothelial cell permeability The large HRP protein is thought to cross primarily via vesicles and fenestrations, whereas the small SF molecule crosses by both paracellular and transcellular routes. Taken with the lack of change in TER and apparent increase in vesicles/fenestrations, these data suggest that VEGF acts by altering transcellular permeability through fenestrations and vesicles.",
author = "Caldwell, {Ruth B} and Y. Feng",
year = "1996",
month = "2",
day = "15",
language = "English (US)",
volume = "37",
journal = "Investigative Ophthalmology and Visual Science",
issn = "0146-0404",
publisher = "Association for Research in Vision and Ophthalmology Inc.",
number = "3",

}

TY - JOUR

T1 - Vascular endothelial growth factor increases endothelial cell permeability in vitro

AU - Caldwell, Ruth B

AU - Feng, Y.

PY - 1996/2/15

Y1 - 1996/2/15

N2 - Purpose. Vascular endothelial growth factor (VEGF) is upregulated in retinal glia during hypoxia, but it is constitutively expressed only by the pigment epithelium in healthy adult retinas. VEGF increases vessel permeability to plasma proteins in vivo. Thus, it may have a role in inducing and maintaining the enhanced permeability of the choriocapillaris endothelium which abuts the pigment epithelium. Methods. We tested this hypothesis and analyzed mechanisms of VEGF-induced permeability alterations using early passage cultures of bovine retinal microvascular endothelial cells and bioassays for permeability, transcellular electrical resistance (TER), and morphology. Results. VEGF treatment induced a rapid and statistically significant increase in permeability to horseradish peroxidase (HRP, 40 kDa) and socium fluorescein (SF, 0.4 KDa). The rate of increase in HRP permeability (66%) was three times that of SF (22%). TER was not affected. Gross morphology of the treated cultures was not altered as indicated by actin localization or scanning electron microscopy. High resolution analysis suggested that the vesicles/fenestrations of the VEGF-treated cells were larger and more abundant as compared with controls. Conclusions. VEGF induces an increase in endothelial cell permeability The large HRP protein is thought to cross primarily via vesicles and fenestrations, whereas the small SF molecule crosses by both paracellular and transcellular routes. Taken with the lack of change in TER and apparent increase in vesicles/fenestrations, these data suggest that VEGF acts by altering transcellular permeability through fenestrations and vesicles.

AB - Purpose. Vascular endothelial growth factor (VEGF) is upregulated in retinal glia during hypoxia, but it is constitutively expressed only by the pigment epithelium in healthy adult retinas. VEGF increases vessel permeability to plasma proteins in vivo. Thus, it may have a role in inducing and maintaining the enhanced permeability of the choriocapillaris endothelium which abuts the pigment epithelium. Methods. We tested this hypothesis and analyzed mechanisms of VEGF-induced permeability alterations using early passage cultures of bovine retinal microvascular endothelial cells and bioassays for permeability, transcellular electrical resistance (TER), and morphology. Results. VEGF treatment induced a rapid and statistically significant increase in permeability to horseradish peroxidase (HRP, 40 kDa) and socium fluorescein (SF, 0.4 KDa). The rate of increase in HRP permeability (66%) was three times that of SF (22%). TER was not affected. Gross morphology of the treated cultures was not altered as indicated by actin localization or scanning electron microscopy. High resolution analysis suggested that the vesicles/fenestrations of the VEGF-treated cells were larger and more abundant as compared with controls. Conclusions. VEGF induces an increase in endothelial cell permeability The large HRP protein is thought to cross primarily via vesicles and fenestrations, whereas the small SF molecule crosses by both paracellular and transcellular routes. Taken with the lack of change in TER and apparent increase in vesicles/fenestrations, these data suggest that VEGF acts by altering transcellular permeability through fenestrations and vesicles.

UR - http://www.scopus.com/inward/record.url?scp=33750160123&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750160123&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33750160123

VL - 37

JO - Investigative Ophthalmology and Visual Science

JF - Investigative Ophthalmology and Visual Science

SN - 0146-0404

IS - 3

ER -