The role of trophoblast cell damage and coagulopathy in the pregnant mice models with preeclamsia-like symptoms

2005 Fiscal Year Final Research Report Summary

• Project/Area Number: 15591739
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: SUGIMURA Motoi Hamamatsu University School of Medicine, Associated Professor, 医学部附属病院, 助教授 (30273189)
• Co-Investigator(Kenkyū-buntansha): KANAYAMA Naohiro Hamamatsu University School of Medicine, Professor, 医学部, 教授 (70204550)
• Project Period (FY): 2003 – 2005
• Keywords: pregnancy-induced hypertension / VEGF / phosphatidylserine / mouse model / preeclamsia

Research Abstract

In order to investigate whether the hypercoagulable state in intervillous space in placenta can induce the preeclampsia-like symptoms, we have focused on the negatively-charged phospholipid microvesicles (phosphatidylserine/phosphatidylcholine PS/PC) and vascular endothelial growth factor (VEGF). Our previous reports have shown that PS/PC microvesicles induce intrauterine growth restriction and that the lack of cyclin-dependent kinase inhibitor, p57kip2, expression in the fetus and the placenta with higher expression of VEGF_<164> plays a role in the development of preeclamsia-like symptoms in pregnant mice.
Here we have established the novel animal experimental models with preeclamsia-like symptoms as follows and the induction of preeclamsia-like symptoms by PS/PC and VEGF indicates that these are related to the pathophysiology of preeclamsia.
1)The artificial PS/PC vesicles induce intrauterine growth restriction with elevations of systolic blood pressure. The elevation of plasma TAT and diffuse fibrin depositions in the placentas indicate enhanced thrombin formation and the significant elevations of SBP can be induced by hypercoagulation in placenta.
2)The exogenous murine VEGF_<164> induce preeclamsia-like symptoms and hypercoagulation in the placental circulation with a significant elevation of SBP. Anti-VEGF neutralized antibody suppresses the elevation of SBP and histological changes in placentas with diffuse fibrin depositions.
These novel animal models established suggest that hypercoagulable state caused by PS/PC derived from activated platelet and VEGF derived from trophblast is important in preeclamsia-like symptoms. The further research on the mechanisms of preeclamsia will be required in these experimental models.