- WITH PREECLAMPSIA: THE INTERSECTION BETWEEN COAGULATION AND INFLAMMATION OFFER EREZ, SUNG-SU KIM, JUNG-SUN KIM, YEON MEE KIM, DEREK E. WILDMAN, NANDOR GABOR THAN, FRANCESCA GOTSCH, JIMMY ESPINOZA, SONIA HASSAN, CHONG JAI KIM, ROBERTO ROMERO, Perinatology Research Branch, NICHD, NIH, DHHS, Detroit, Michigan, Wayne State University School of Medicine, Department of Pathology, Detroit, Michigan, Wayne State University, Center for Molecular Medicine & Genetics, Detroit, Michigan, Wayne State University School of Medicine, Department of Obstetrics and Gynecology, Detroit, Michigan OBJECTIVE: Preeclampsia (PE) is characterized by excessive thrombin generation, which has been implicated in the multiple organ damage associated with the disease. Protease activated receptor-1 (PAR-1), a G-protein receptor, mediates the biological effects of thrombin on coagulation and its proinflammatory properties. The aim of this study was to determine the expression of PAR-1 in placentas from women with PE as well as from patients with preterm labor (PTL) without inflammation. STUDY DESIGN: A cross sectional study was designed including two study groups matched for gestational age at delivery: 1) preterm PE (!35 weeks gestation; n=27) and 2) PTL without inflammation (n=27). Placental tissues were immunostained for PAR-1 using a monoclonal anti-PAR-1 antibody. Placental tissue microarrays were constructed using an automated tissue arrayer and a standard 0.6 mm microarray needle. Immunoreactivity of PAR1 in the villous trophoblasts was graded as: 0, negative; 1, weakly positive; and 2, strongly positive. RESULTS: 1) Protein expression of PAR-1 was found in the cellular compartments of the placental villous tree, mainly in villous trophoblasts and stromal endothelial cells; 2) PAR-1 was detected in 92.6% (25/27) of the placentas of PE women and in 88.9% (24/27) of the placentas from the control group; and 3) The rate of strong positive PAR-1 immunostaining was significantly higher in placentas of PE patients than placentas from the control group [36% (9/25) vs. 8.3% (2/24); p=0.037, respectively]. CONCLUSION: Placentas from pregnancies complicated by preterm PE have significantly higher expression of immunoreactive PAR-1 than placentas from women with spontaneous PTL. This observation is consistent with a role for PAR-1 as a mediator of thrombin’s effect on coagulation and inflammation. We propose that the effects of thrombin in PE are due to increased thrombin generation and higher expression of the major receptor for this enzyme.