Murine rVEGF164b, an inhibitory VEGF reduces VEGF-A-dependent endothelial proliferation and barrier dysfunction

Walter Cromer, Merilyn H. Jennings, Yoshinubo Odaka, James Michael Mathis, J. Steven Alexander

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10 Citations (Scopus)

Abstract

Objective: To investigate the effects of the murine inhibitory vascular endothelial growth factor (VEGF, rVEGF164b), we generated an adenoviral vector encoding rVEGF164b, and examined its effects on endothelial barrier, growth, and structure. Method: Mouse vascular endothelial cells (MVEC) proliferation was determined by an MTT assay. Barrier of MVEC monolayers was measured by trans-endothelial electrical resistance (TEER). Reorganization of actin and zonula occludens-1 (ZO-1) were determined by fluorescent microscopy. Results: Mouse venous endothelial cells treated with murine VEGF-A (VEGF-A) (50 ng/mL) increased proliferation (60.7 ± 0.1%) within 24 hours (p < 0.05) and rVEGF164b inhibited VEGF-A-induced proliferation. TEER was significantly decreased by VEGF-A (81.7 ± 6.2% of control). Treatment with rVEGF164b at 50 ng/mL transiently reduced MVEC barrier (p < 0.05) at 30 minutes post-treatment (87.9 ± 1.7% of control TEER), and returned to control levels by 40 minutes post-treatment. Treatment with rVEGF164b prevented barrier changes by subsequent exposure to VEGF-A. Treatment of MVECS with VEGF-A reorganized F-actin and ZO-1, which was attenuated by rVEGF164b. Conclusions: VEGF-A may dysregulate endothelial barrier through junctional cytoskeleton processes, which can be attenuated by rVEGF164b. The VEGF-A stimulated MVEC proliferation, barrier dysregulation, and cytoskeletal rearrangement. However, rVEGF164b blocks these effects, therefore it may be useful for regulation studies of VEGFA/VEGF-R signaling in many different models.

Original languageEnglish
Pages (from-to)536-547
Number of pages12
JournalMicrocirculation
Volume17
Issue number7
DOIs
StatePublished - 1 Oct 2010

Fingerprint

Vascular Endothelial Growth Factor A
Endothelial Cells
Electric Impedance
Tight Junctions
Actins
Cell Proliferation
Cytoskeleton
Microscopy
Growth

Keywords

  • Barrier
  • Endothelial
  • Inhibitory
  • Migration
  • Proliferation
  • VEGF-A
  • VEGF164b

Cite this

Cromer, Walter ; Jennings, Merilyn H. ; Odaka, Yoshinubo ; Mathis, James Michael ; Alexander, J. Steven. / Murine rVEGF164b, an inhibitory VEGF reduces VEGF-A-dependent endothelial proliferation and barrier dysfunction. In: Microcirculation. 2010 ; Vol. 17, No. 7. pp. 536-547.
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abstract = "Objective: To investigate the effects of the murine inhibitory vascular endothelial growth factor (VEGF, rVEGF164b), we generated an adenoviral vector encoding rVEGF164b, and examined its effects on endothelial barrier, growth, and structure. Method: Mouse vascular endothelial cells (MVEC) proliferation was determined by an MTT assay. Barrier of MVEC monolayers was measured by trans-endothelial electrical resistance (TEER). Reorganization of actin and zonula occludens-1 (ZO-1) were determined by fluorescent microscopy. Results: Mouse venous endothelial cells treated with murine VEGF-A (VEGF-A) (50 ng/mL) increased proliferation (60.7 ± 0.1{\%}) within 24 hours (p < 0.05) and rVEGF164b inhibited VEGF-A-induced proliferation. TEER was significantly decreased by VEGF-A (81.7 ± 6.2{\%} of control). Treatment with rVEGF164b at 50 ng/mL transiently reduced MVEC barrier (p < 0.05) at 30 minutes post-treatment (87.9 ± 1.7{\%} of control TEER), and returned to control levels by 40 minutes post-treatment. Treatment with rVEGF164b prevented barrier changes by subsequent exposure to VEGF-A. Treatment of MVECS with VEGF-A reorganized F-actin and ZO-1, which was attenuated by rVEGF164b. Conclusions: VEGF-A may dysregulate endothelial barrier through junctional cytoskeleton processes, which can be attenuated by rVEGF164b. The VEGF-A stimulated MVEC proliferation, barrier dysregulation, and cytoskeletal rearrangement. However, rVEGF164b blocks these effects, therefore it may be useful for regulation studies of VEGFA/VEGF-R signaling in many different models.",
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Murine rVEGF164b, an inhibitory VEGF reduces VEGF-A-dependent endothelial proliferation and barrier dysfunction. / Cromer, Walter; Jennings, Merilyn H.; Odaka, Yoshinubo; Mathis, James Michael; Alexander, J. Steven.

In: Microcirculation, Vol. 17, No. 7, 01.10.2010, p. 536-547.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Murine rVEGF164b, an inhibitory VEGF reduces VEGF-A-dependent endothelial proliferation and barrier dysfunction

AU - Cromer, Walter

AU - Jennings, Merilyn H.

AU - Odaka, Yoshinubo

AU - Mathis, James Michael

AU - Alexander, J. Steven

PY - 2010/10/1

Y1 - 2010/10/1

N2 - Objective: To investigate the effects of the murine inhibitory vascular endothelial growth factor (VEGF, rVEGF164b), we generated an adenoviral vector encoding rVEGF164b, and examined its effects on endothelial barrier, growth, and structure. Method: Mouse vascular endothelial cells (MVEC) proliferation was determined by an MTT assay. Barrier of MVEC monolayers was measured by trans-endothelial electrical resistance (TEER). Reorganization of actin and zonula occludens-1 (ZO-1) were determined by fluorescent microscopy. Results: Mouse venous endothelial cells treated with murine VEGF-A (VEGF-A) (50 ng/mL) increased proliferation (60.7 ± 0.1%) within 24 hours (p < 0.05) and rVEGF164b inhibited VEGF-A-induced proliferation. TEER was significantly decreased by VEGF-A (81.7 ± 6.2% of control). Treatment with rVEGF164b at 50 ng/mL transiently reduced MVEC barrier (p < 0.05) at 30 minutes post-treatment (87.9 ± 1.7% of control TEER), and returned to control levels by 40 minutes post-treatment. Treatment with rVEGF164b prevented barrier changes by subsequent exposure to VEGF-A. Treatment of MVECS with VEGF-A reorganized F-actin and ZO-1, which was attenuated by rVEGF164b. Conclusions: VEGF-A may dysregulate endothelial barrier through junctional cytoskeleton processes, which can be attenuated by rVEGF164b. The VEGF-A stimulated MVEC proliferation, barrier dysregulation, and cytoskeletal rearrangement. However, rVEGF164b blocks these effects, therefore it may be useful for regulation studies of VEGFA/VEGF-R signaling in many different models.

AB - Objective: To investigate the effects of the murine inhibitory vascular endothelial growth factor (VEGF, rVEGF164b), we generated an adenoviral vector encoding rVEGF164b, and examined its effects on endothelial barrier, growth, and structure. Method: Mouse vascular endothelial cells (MVEC) proliferation was determined by an MTT assay. Barrier of MVEC monolayers was measured by trans-endothelial electrical resistance (TEER). Reorganization of actin and zonula occludens-1 (ZO-1) were determined by fluorescent microscopy. Results: Mouse venous endothelial cells treated with murine VEGF-A (VEGF-A) (50 ng/mL) increased proliferation (60.7 ± 0.1%) within 24 hours (p < 0.05) and rVEGF164b inhibited VEGF-A-induced proliferation. TEER was significantly decreased by VEGF-A (81.7 ± 6.2% of control). Treatment with rVEGF164b at 50 ng/mL transiently reduced MVEC barrier (p < 0.05) at 30 minutes post-treatment (87.9 ± 1.7% of control TEER), and returned to control levels by 40 minutes post-treatment. Treatment with rVEGF164b prevented barrier changes by subsequent exposure to VEGF-A. Treatment of MVECS with VEGF-A reorganized F-actin and ZO-1, which was attenuated by rVEGF164b. Conclusions: VEGF-A may dysregulate endothelial barrier through junctional cytoskeleton processes, which can be attenuated by rVEGF164b. The VEGF-A stimulated MVEC proliferation, barrier dysregulation, and cytoskeletal rearrangement. However, rVEGF164b blocks these effects, therefore it may be useful for regulation studies of VEGFA/VEGF-R signaling in many different models.

KW - Barrier

KW - Endothelial

KW - Inhibitory

KW - Migration

KW - Proliferation

KW - VEGF-A

KW - VEGF164b

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U2 - 10.1111/j.1549-8719.2010.00047.x

DO - 10.1111/j.1549-8719.2010.00047.x

M3 - Article

VL - 17

SP - 536

EP - 547

JO - Microcirculation

JF - Microcirculation

SN - 1073-9688

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