The Role And Mechanism Of 15-hydroxyeicosatetraenoic Acid In Placental Trophoblast

Preeclampsia(PE)is a multi-system dysfunction disease that occurs after 20 gestational weeks,which affected about 5%-8% of pregnant women worldwide every year,and is the disease with the highest mortality rate of pregnant women and newborns.The clinical manifestations of PE mainly include hypertension and proteinuria.Although relevant studies on preeclampsia has made significant progress,but its etiology and pathology mechanism is still unclear now,and it is still the important hot issue to be study in this field.In our previous research,the detection method of 15-hydroxyeicosatetraenoic acid(15-HETE)was established using ultra-high pressure liquid chromatography tandem six-pole mass spectrometry.Thus this study was focused on : 15-HETE is whether involved in the biological process of human uterine spiral artery remodeling process and its effects of chorionic trophoblast-mediated apoptosis of uterine microvascular endothelial cells(EAhy926).The roles of 15-HETE on arterial remodeling disorders may provide new understanding of the etiology of preeclampsia.Method:1.Collected serum samples of pregnant women during the whole process of obstetric examination and established a PE biological sample library.2.using 15-HETE and matrix metalloproteinase 2(MMP-2)inhibitors to treat HTR8/SVneo and EAhy926.The migration and invasion ability of HTR8/SVneo was determined using transwell chamber.3.Apoptosis of EAhy926 were detected using Annexin V / PI double staining-flow cytometry.4.MMP2 expression was measured by Western blotting.Result:1.The 15-HETE in preeclampsia pregnant women is significantly higher than that in normal pregnant women,and the serous 15-HETE in the severe preeclampsia group is significantly higher than that in the mild preeclampsia group,pregnancy-induced hypertension group and control group.2.15-HETE promoted migration and invasion of HTR8/ SVneo.And 15-HETE has promoting effect on apoptosis of EAhy926.3.The expression of MMP2 in HTR8/SVneo was improved when treated with 15-HETE.In EAhy926.,the protein expression of MMP2 showed no significant changes with 15-HETE treatment.Conclusion:1.15-HETE in maternal serum may affect the remodeling process of spiral uterine arteries in preeclampsia.2.15-HETE may play a role in the etiology of preeclampsia by promoted the migration and invasion of trophoblastic cells via MMP2.