Over-expression of the thrombin receptor (PAR-1) in the placenta in preeclampsia: A mechanism for the intersection of coagulation and inflammation

Offer Erez, Roberto Romero, Sung Su Kim, Jung Sun Kim, Yeon Mee Kim, Derek E. Wildman, Nandor Gabor Than, Shali Mazaki-Tovi, Francesca Gotsch, Beth Pineles, Juan Pedro Kusanovic, Jimmy Espinoza, Pooja Mittal, Moshe Mazor, Sonia S. Hassan, Chong Jai Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Objective. Preeclampsia (PE) is characterized by excessive thrombin generation, which has been implicated in the multiple organ damage associated with the disease. The biological effects of thrombin on coagulation and inflammation are mediated by protease-activated receptor-1 (PAR-1), a G protein-coupled receptor. The aim of this study was to determine whether preterm PE is associated with changes in placental expression of PAR-1. Study design. This cross-sectional study included two groups matched for gestational age at delivery: (1) patients with preterm PE (<37 weeks of gestation; n = 26) and (2) a control group of patients with preterm labor without intra-amniotic infection (n = 26). Placental tissue microarrays were immunostained for PAR-1. Immunoreactivity of PAR-1 in the villous trophoblasts was graded as negative, weak-positive, or strong-positive. Results. (1) The proportion of cases with strong PAR-1 immunoreactivity was significantly higher in placentas of patients with PE than in placentas from the control group (37.5% (9/24) vs. 8.7% (2/23); p = 0.036, respectively). (2) PAR-1 immunoreactivity was found in the cellular compartments of the placental villous tree, mainly in villous trophoblasts and stromal endothelial cells. (3) PAR-1 was detected in 92.3% (24/26) of the placentas of women with PE and in 88.5% (23/26) of the placentas from the control group. Conclusion. Placentas from pregnancies complicated by preterm PE had a significantly higher frequency of strong PAR-1 expression than placentas from women with spontaneous preterm labor. This observation is consistent with a role for PAR-1 as a mediator of the effect of thrombin on coagulation and inflammation in PE. We propose that the effects of thrombin in PE are due to increased thrombin generation and higher expression of PAR-1, the major receptor for this enzyme.

Original languageEnglish (US)
Pages (from-to)345-355
Number of pages11
JournalJournal of Maternal-Fetal and Neonatal Medicine
Volume21
Issue number6
DOIs
StatePublished - 2008

Keywords

  • Immunohistochemistry
  • PAR-1
  • Preterm
  • Tethered ligand
  • Trophoblast
  • Villous infarct

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Obstetrics and Gynecology

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