Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells

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Abstract

Introduction Soluble fms-like tyrosine kinase-1 (sFlt-1) is a vascular endothelial growth factor (VEGF) binding protein and potent antagonist of VEGF. Alpha 2 macroglobulin (α2M) is another major binding protein for circulating VEGF, which is present in human plasma at higher concentration (2-4 mg/mL) than sFlt-1. This study investigated the effects of sFlt-1 and α2M on VEGF-induced endothelin-1 (ET-1) upregulation in human microvascular endothelial cell-1 (HMEC-1). Methods HMEC-1 was cultured and incubated with varying concentrations of sFlt-1 and α2M in combination with VEGF. ET-1 mRNA expression in the cells was measured by real time RT-PCR and ET-1 protein by western blot analysis. Results ET-1 expression in HMEC-1 incubated with VEGF significantly increased in time- and dose-dependent manners. Next, HMEC-1 was treated with the sFlt-1 (10-1000 ng/mL) or α2M (10-10000 ng/mL) in the presence of VEGF (10 ng/mL). We found that sFlt-1 induced a significant decrease of ET-1 expression upregulated by VEGF, while α2M did not affect the VEGF-induced ET-1 expression. Conclusions sFLT-1 suppressed the VEGF-induced the ET-1 expression of HMEC-1. However, α2M did not show a significant effect on the ET-1 expression that was induced by VEGF. The results suggest that a certain proportion of the bound form α2M-VEGF have a biological action involved in the pathophysiology of preeclampsia.

Original languageEnglish
Pages (from-to)64-69
Number of pages6
JournalPlacenta
Volume35
Issue number1
DOIs
Publication statusPublished - 2014 Jan 1

Fingerprint

alpha-Macroglobulins
Vascular Endothelial Growth Factor Receptor-1
Endothelin-1
Vascular Endothelial Growth Factor A
Up-Regulation
Endothelial Cells
Macroglobulins
Receptor, Fibroblast Growth Factor, Type 1
Carrier Proteins
Pre-Eclampsia
Real-Time Polymerase Chain Reaction

Keywords

  • Endothelin-1
  • Preeclampsia
  • sFlt-1

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Reproductive Medicine
  • Developmental Biology

Cite this

@article{3caebc3f81814c84885e2b17f85dfd89,
title = "Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells",
abstract = "Introduction Soluble fms-like tyrosine kinase-1 (sFlt-1) is a vascular endothelial growth factor (VEGF) binding protein and potent antagonist of VEGF. Alpha 2 macroglobulin (α2M) is another major binding protein for circulating VEGF, which is present in human plasma at higher concentration (2-4 mg/mL) than sFlt-1. This study investigated the effects of sFlt-1 and α2M on VEGF-induced endothelin-1 (ET-1) upregulation in human microvascular endothelial cell-1 (HMEC-1). Methods HMEC-1 was cultured and incubated with varying concentrations of sFlt-1 and α2M in combination with VEGF. ET-1 mRNA expression in the cells was measured by real time RT-PCR and ET-1 protein by western blot analysis. Results ET-1 expression in HMEC-1 incubated with VEGF significantly increased in time- and dose-dependent manners. Next, HMEC-1 was treated with the sFlt-1 (10-1000 ng/mL) or α2M (10-10000 ng/mL) in the presence of VEGF (10 ng/mL). We found that sFlt-1 induced a significant decrease of ET-1 expression upregulated by VEGF, while α2M did not affect the VEGF-induced ET-1 expression. Conclusions sFLT-1 suppressed the VEGF-induced the ET-1 expression of HMEC-1. However, α2M did not show a significant effect on the ET-1 expression that was induced by VEGF. The results suggest that a certain proportion of the bound form α2M-VEGF have a biological action involved in the pathophysiology of preeclampsia.",
keywords = "Endothelin-1, Preeclampsia, sFlt-1",
author = "Yi, {Kyong Wook} and Jung, {S. H.} and Geum-Joon Cho and Seol, {H. J.} and Hong, {Soon Cheol} and Oh, {Min Jeong} and Kim, {Hai Joong}",
year = "2014",
month = "1",
day = "1",
doi = "10.1016/j.placenta.2013.09.008",
language = "English",
volume = "35",
pages = "64--69",
journal = "Placenta",
issn = "0143-4004",
publisher = "W.B. Saunders Ltd",
number = "1",

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TY - JOUR

T1 - Effects of sFlt-1 and alpha 2-macroglobulin on vascular endothelial growth factor-induced endothelin-1 upregulation in human microvascular endothelial cells

AU - Yi, Kyong Wook

AU - Jung, S. H.

AU - Cho, Geum-Joon

AU - Seol, H. J.

AU - Hong, Soon Cheol

AU - Oh, Min Jeong

AU - Kim, Hai Joong

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Introduction Soluble fms-like tyrosine kinase-1 (sFlt-1) is a vascular endothelial growth factor (VEGF) binding protein and potent antagonist of VEGF. Alpha 2 macroglobulin (α2M) is another major binding protein for circulating VEGF, which is present in human plasma at higher concentration (2-4 mg/mL) than sFlt-1. This study investigated the effects of sFlt-1 and α2M on VEGF-induced endothelin-1 (ET-1) upregulation in human microvascular endothelial cell-1 (HMEC-1). Methods HMEC-1 was cultured and incubated with varying concentrations of sFlt-1 and α2M in combination with VEGF. ET-1 mRNA expression in the cells was measured by real time RT-PCR and ET-1 protein by western blot analysis. Results ET-1 expression in HMEC-1 incubated with VEGF significantly increased in time- and dose-dependent manners. Next, HMEC-1 was treated with the sFlt-1 (10-1000 ng/mL) or α2M (10-10000 ng/mL) in the presence of VEGF (10 ng/mL). We found that sFlt-1 induced a significant decrease of ET-1 expression upregulated by VEGF, while α2M did not affect the VEGF-induced ET-1 expression. Conclusions sFLT-1 suppressed the VEGF-induced the ET-1 expression of HMEC-1. However, α2M did not show a significant effect on the ET-1 expression that was induced by VEGF. The results suggest that a certain proportion of the bound form α2M-VEGF have a biological action involved in the pathophysiology of preeclampsia.

AB - Introduction Soluble fms-like tyrosine kinase-1 (sFlt-1) is a vascular endothelial growth factor (VEGF) binding protein and potent antagonist of VEGF. Alpha 2 macroglobulin (α2M) is another major binding protein for circulating VEGF, which is present in human plasma at higher concentration (2-4 mg/mL) than sFlt-1. This study investigated the effects of sFlt-1 and α2M on VEGF-induced endothelin-1 (ET-1) upregulation in human microvascular endothelial cell-1 (HMEC-1). Methods HMEC-1 was cultured and incubated with varying concentrations of sFlt-1 and α2M in combination with VEGF. ET-1 mRNA expression in the cells was measured by real time RT-PCR and ET-1 protein by western blot analysis. Results ET-1 expression in HMEC-1 incubated with VEGF significantly increased in time- and dose-dependent manners. Next, HMEC-1 was treated with the sFlt-1 (10-1000 ng/mL) or α2M (10-10000 ng/mL) in the presence of VEGF (10 ng/mL). We found that sFlt-1 induced a significant decrease of ET-1 expression upregulated by VEGF, while α2M did not affect the VEGF-induced ET-1 expression. Conclusions sFLT-1 suppressed the VEGF-induced the ET-1 expression of HMEC-1. However, α2M did not show a significant effect on the ET-1 expression that was induced by VEGF. The results suggest that a certain proportion of the bound form α2M-VEGF have a biological action involved in the pathophysiology of preeclampsia.

KW - Endothelin-1

KW - Preeclampsia

KW - sFlt-1

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U2 - 10.1016/j.placenta.2013.09.008

DO - 10.1016/j.placenta.2013.09.008

M3 - Article

C2 - 24231447

AN - SCOPUS:84896542289

VL - 35

SP - 64

EP - 69

JO - Placenta

JF - Placenta

SN - 0143-4004

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