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

Affiliation

Implantation and Placental Development Laboratory, Centre for Reproductive Health, Hudson Institute of Medical Research, Clayton, VIC, Australia; Department of Molecular and Translational Science, Monash University, Clayton, VIC, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia. Electronic address: [Email]

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,VE-Cadherin,Vascular permeability,