Thrombomodulin (TM) and endothelial protein C receptor (EPCR) are members of the protein Canticoagulant pathway, involved in hemostasis and inflammation in the vascular bed. We evaluated the role of TM/EPCR in non-pregnant women (NP), healthy pregnant women (HP), women with gestation vascular complications (GVC) and LMWH-treated pregnant females. TM/EPCR gene expression and antigen levels were examined in patient samples (placental sections and circulating microvesicles [MVs]), human umbilical vein endothelial cells (HUVEC) and trophoblasts, using quantitative PCR, flow cytometry and fluorescent microscopy methods.
HUVEC and trophoblasts expressed high levels of EPCR (~80%) which decreased in their related MVs (25-40%). TM expression on 24-week gestation trophoblasts was ~25% and increased to ~60% in term placental trophoblasts. TM antigen could not be detected on HUVEC or trophoblast MVs. TM gene expression decreased in placentas of the GVC cohort compared to the HP and restored in the LMWH-treated group. Circulating MVs expressed moderate levels of EPCR (~30%) without significant differences between HP, GVC and NP groups. Surprisingly, we failed to find TM in circulating MVs of study cohorts
However, MVs from study groups increased TM and EPCR gene expression and TM antigen levels on HUVEC relative to untreated cells.
MVs of the GVC group reduced EPCR antigen level on trophoblasts compared to untreated cells.
Conclusion: Decrease in TM expression related to pregnancy complications, effect of GVCMVs. 1,2,, Rami Sammour 3, Yaniv Zipori4, Naomi Lanir1,2, Benjamin Brenner1,2, Anat Aharon 1,2.
Bruce Rappaport Faculty of Medicine, Technion Haifa, Israel
1. Thrombosis and Hemostasis Unit,Dept. of Hematology, Rambam Health Care Campus, Haifa, Israel
2. Dept. of Obstetrics and Gynecology, Bnai-Zion Medical Center, Haifa, Israel
3. Dept. of Obstetrics and Gynecology4, Rambam Health Care Campus, Haifa, Israel