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.
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.
Authors: Li Ma; Rafael Perini; Webb McKnight; Michael Dicay; Andre Klein; Morley D Hollenberg; John L Wallace Journal: Proc Natl Acad Sci U S A Date: 2004-12-22 Impact factor: 11.205
Authors: Richard J Levine; Ravi Thadhani; Cong Qian; Chun Lam; Kee-Hak Lim; Kai F Yu; Anastasia L Blink; Benjamin P Sachs; Franklin H Epstein; Baha M Sibai; Vikas P Sukhatme; S Ananth Karumanchi Journal: JAMA Date: 2005-01-05 Impact factor: 56.272
Authors: Myles Wolf; Carl A Hubel; Chun Lam; Marybeth Sampson; Jeffrey L Ecker; Roberta B Ness; Augustine Rajakumar; Ashi Daftary; Alia S M Shakir; Ellen W Seely; James M Roberts; Vikas P Sukhatme; S Ananth Karumanchi; Ravi Thadhani Journal: J Clin Endocrinol Metab Date: 2004-12 Impact factor: 5.958
Authors: Pooja Mittal; Roberto Romero; Adi L Tarca; Sorin Draghici; Chia-Ling Nhan-Chang; Tinnakorn Chaiworapongsa; John Hotra; Ricardo Gomez; Juan Pedro Kusanovic; Deug-Chan Lee; Chong Jai Kim; Sonia S Hassan Journal: Am J Obstet Gynecol Date: 2011-02 Impact factor: 8.661
Authors: Pooja Mittal; Roberto Romero; Adi L Tarca; Juan Gonzalez; Sorin Draghici; Yi Xu; Zhong Dong; Chia-Ling Nhan-Chang; Tinnakorn Chaiworapongsa; Stephen Lye; Juan Pedro Kusanovic; Leonard Lipovich; Shali Mazaki-Tovi; Sonia S Hassan; Sam Mesiano; Chong Jai Kim Journal: J Perinat Med Date: 2010-07-14 Impact factor: 1.901
Authors: Piya Chaemsaithong; Roberto Romero; Adi L Tarca; Steven J Korzeniewski; Alyse G Schwartz; Jezid Miranda; Ahmed I Ahmed; Zhong Dong; Sonia S Hassan; Lami Yeo; Tinnakorn Tinnakorn Journal: J Matern Fetal Neonatal Med Date: 2014-09-29
Authors: Guadalupe Estrada-Gutierrez; Renato E Cappello; Nikita Mishra; Roberto Romero; Jerome F Strauss; Scott W Walsh Journal: Am J Pathol Date: 2010-12-23 Impact factor: 4.307
Authors: Tinnakorn Chaiworapongsa; Roberto Romero; Steven J Korzeniewski; Josef M Cortez; Athina Pappas; Adi L Tarca; Piya Chaemsaithong; Zhong Dong; Lami Yeo; Sonia S Hassan Journal: J Matern Fetal Neonatal Med Date: 2013-08-08