Elevated protease HtrA4 in the maternal circulation of preeclampsia may contribute to endothelial barrier disruption by cleaving key junctional protein VE-cadherin

Esther Tseng, Sonia Soo Yee Teoh, Yao Wang, Guiying Nie

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Preeclampsia is hallmarked by systemic endothelial dysfunction, including increased endothelial permeability and oedema. Placenta-derived factors in maternal blood contribute to endothelial barrier impairment, but molecular mechanisms are unclear. HtrA4 is a placenta-specific protease that is secreted into the maternal circulation and elevated in early-onset preeclampsia. In this study, we found HtrA4 cleaved the key endothelial junctional protein VE-cadherin in vitro. HtrA4 at concentrations found in preeclampsia also cleaved VE-cadherin in HUVECs as an endothelial model, disrupted cell-cell connections and induced intercellular gaps. These results provide critical insights into understanding the molecular mechanisms of endothelial barrier disruption in preeclampsia.

Original languageEnglish
Number of pages3
JournalPlacenta
DOIs
Publication statusAccepted/In press - 1 Jan 2019

Keywords

  • Endothelial barrier
  • HtrA4
  • Oedema
  • Preeclampsia
  • Vascular permeability
  • VE-Cadherin

Cite this

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title = "Elevated protease HtrA4 in the maternal circulation of preeclampsia may contribute to endothelial barrier disruption by cleaving key junctional protein VE-cadherin",
abstract = "Preeclampsia is hallmarked by systemic endothelial dysfunction, including increased endothelial permeability and oedema. Placenta-derived factors in maternal blood contribute to endothelial barrier impairment, but molecular mechanisms are unclear. HtrA4 is a placenta-specific protease that is secreted into the maternal circulation and elevated in early-onset preeclampsia. In this study, we found HtrA4 cleaved the key endothelial junctional protein VE-cadherin in vitro. HtrA4 at concentrations found in preeclampsia also cleaved VE-cadherin in HUVECs as an endothelial model, disrupted cell-cell connections and induced intercellular gaps. These results provide critical insights into understanding the molecular mechanisms of endothelial barrier disruption in preeclampsia.",
keywords = "Endothelial barrier, HtrA4, Oedema, Preeclampsia, Vascular permeability, VE-Cadherin",
author = "Esther Tseng and {Yee Teoh}, {Sonia Soo} and Yao Wang and Guiying Nie",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.placenta.2019.01.001",
language = "English",
journal = "Placenta",
issn = "0143-4004",
publisher = "W.B. Saunders",

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Elevated protease HtrA4 in the maternal circulation of preeclampsia may contribute to endothelial barrier disruption by cleaving key junctional protein VE-cadherin. / Tseng, Esther; Yee Teoh, Sonia Soo; Wang, Yao; Nie, Guiying.

In: Placenta, 01.01.2019.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Elevated protease HtrA4 in the maternal circulation of preeclampsia may contribute to endothelial barrier disruption by cleaving key junctional protein VE-cadherin

AU - Tseng, Esther

AU - Yee Teoh, Sonia Soo

AU - Wang, Yao

AU - Nie, Guiying

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Preeclampsia is hallmarked by systemic endothelial dysfunction, including increased endothelial permeability and oedema. Placenta-derived factors in maternal blood contribute to endothelial barrier impairment, but molecular mechanisms are unclear. HtrA4 is a placenta-specific protease that is secreted into the maternal circulation and elevated in early-onset preeclampsia. In this study, we found HtrA4 cleaved the key endothelial junctional protein VE-cadherin in vitro. HtrA4 at concentrations found in preeclampsia also cleaved VE-cadherin in HUVECs as an endothelial model, disrupted cell-cell connections and induced intercellular gaps. These results provide critical insights into understanding the molecular mechanisms of endothelial barrier disruption in preeclampsia.

AB - Preeclampsia is hallmarked by systemic endothelial dysfunction, including increased endothelial permeability and oedema. Placenta-derived factors in maternal blood contribute to endothelial barrier impairment, but molecular mechanisms are unclear. HtrA4 is a placenta-specific protease that is secreted into the maternal circulation and elevated in early-onset preeclampsia. In this study, we found HtrA4 cleaved the key endothelial junctional protein VE-cadherin in vitro. HtrA4 at concentrations found in preeclampsia also cleaved VE-cadherin in HUVECs as an endothelial model, disrupted cell-cell connections and induced intercellular gaps. These results provide critical insights into understanding the molecular mechanisms of endothelial barrier disruption in preeclampsia.

KW - Endothelial barrier

KW - HtrA4

KW - Oedema

KW - Preeclampsia

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