[PS 01-19] INHIBITING PROTEASE-ACTIVATED RECEPTOR 2 ALLEVIATED PREECLAMPSIA

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Abstract

Objective:

Preeclampsia (PE) is pregnancy-induced hypertension with proteinuria that develops in 2∼5% of pregnancy, and is a cause of premature delivery and fetal growth restriction. Pathogenesis of PE still remains to be clarified, and its treatment other than delivery and removal of placenta is not established. Inflammation and hypercoagulability are often seen in PE.

Objective:

Protease-activated receptor (PAR) is activated by blood coagulation factors, and modulates inflammation, blood coagulation, and vascular function. PAR1 and PAR2 are involved in inflammation, but their role in PE is not clear.

Objective:

Homozygous lack of PAR1 is embryonic lethal, whereas homozygous PAR2-/- mice breed well without any problem. The purpose of the present study is to clarify the role of PAR2 in PE and whether PAR2 could be a target of PE treatment.

Design and Method:

Pregnant PAR2-/- mice or wild type pregnant mice treated with a PAR2 antagonist ENMD-1068 (50 mg/kg/d i.p. from 13.5 dpc to 17.5 dpc) were administered i.p. with low dose LPS (20 μg/kg/d on 14.5 dpc and 80 μg/kg/d on 15.5 dpc-17.5 dpc) to produce PE model, and their BP and fetal weights were compared with controls.

Results:

Lack or inhibition of PAR2 alleviated hypertension and fetal growth-restriction. PAR2 agonist-increased inflammatory gene expression in a trophoblast cell line in vitro.

Conclusions:

PAR2 is likely to be a target of PE and fetal growth restriction associated with PE.

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