Elucidation of pathophysiology and development of new therapeutic agents for preeclampsia through complement inhibition

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16770
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Osaka University
• Principal Investigator: Mimura Kazuya 大阪大学, 医学系研究科, 助教 (50437422)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 妊娠高血圧症候群 / 補体 / ヒト臍帯血管内皮細胞 / 予知・予後予測マーカー

Outline of Final Research Achievements

We investigated whether complement activity is involved in the pathology of preeclampsia in human samples, and elucidated a new mechanism by utilizing the preeclampsia maternal vascular endothelium model using human umbilical cord vascular endothelial cells. The other purpose was to comprehensively screen new drugs that can improve vascular endothelial damage via complement inhibitory action by adding to the model. As an in vivo study, we searched for complement markers in serum and urine to determine whether complement could be a predictive and prognostic marker for preeclampsia, and investigated complement activity in preeclampsia cases. In addition, we have conducted a comprehensive screening using a library of Kampo drugs using an in vitro preeclampsia model to narrow down candidate drugs.

Free Research Field

妊娠高血圧症候群

Academic Significance and Societal Importance of the Research Achievements

妊娠高血圧症候群の中でも妊娠高血圧腎症は、妊娠20週以降に発症する高血圧、尿蛋白、他の全身障害を特徴とした疾患で、胎児死亡・母体死亡の主な原因である。全妊娠の5-8%に発症する高い頻度に加え、現在、分娩年齢の高齢化に伴い増加している。日本における妊娠高血圧症候群も最近Hypertensive Disorders of Pregnancy（HDP）と改名され、HDPはけして軽症な病態はなく、すぐに治療に取り掛かるべき疾患であるという啓発が進んでいる。いまだ治療は分娩のみで薬物療法は確立していない。母体健康・胎児健康のためにも、治療薬の開発に寄与することは現在の周産期医学において非常に重要である。