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
Pages (from-to)51-53
Number of pages3
JournalPlacenta
Volume76
Issue number15
DOIs
Publication statusPublished - 15 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",
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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, Vol. 76, No. 15, 15.01.2019, p. 51-53.

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

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Y1 - 2019/1/15

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.

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KW - HtrA4

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