2020 Fiscal Year Final Research Report
Application of nanomedicine therapy for hypertensive disorders of pregnancy focusing on the molecular mechanisms related to oxidative stress regulation the placenta
| Project/Area Number |
18H02943
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 56040:Obstetrics and gynecology-related
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
Fujii Tomoyuki 東京大学, 医学部附属病院, 届出研究員 (40209010)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
廣田 泰 東京大学, 医学部附属病院, 准教授 (40598653)
永松 健 東京大学, 医学部附属病院, 准教授 (60463858)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Keywords | 妊娠 / 妊娠高血圧症候群 / マウスモデル / 絨毛細胞 / 胎盤 / リゾフォスファチジン酸 |
|---|
| Outline of Final Research Achievements |
We analyzed the pathoetiology of hypertensive disorders of pregnancy (HDP) focusing on the relevance of lysophosphatidic acid (LPA) signaling pathway to placental oxidative stress. We revealed that LPA signaling is involved in the regulation of placental oxidative stress with alteration in the production of autotaxin (ATX), an LPA-producing enzyme, and that dysregulation in this signaling is a hidden mechanism for the development of HDP.
We explored the therapeutic potential of nanomedicine for HDP focusing on oxidative stress. The optimal conditions of nano-micelle carrier which can avoid placental transfer were determined. Expecting anti-oxidative stress efficacy. statins encapsulated in the carrier were administered to HDP mouse models. Consequently, hypertension and fetal growth were improved. Statin-micelle carrier can be a novel therapeutic approach for HDP without fetal toxicity.
|
| Free Research Field |
周産期医学
|
| Academic Significance and Societal Importance of the Research Achievements |
妊娠高血圧症候群(HDP)は胎盤の機能破綻に伴って生じ、胎盤内の酸化ストレスの集積が機能破綻に関与する因子として指摘されてきた。本研究は、LPAシグナル経路と胎盤の酸化ストレスの関係を解明し、脂質メディエーターによる酸化ストレス制御というHDPの病態理解に新たな視点を与えた。さらに、本研究は胎児毒性の危険性がある薬剤について胎盤通過性の問題についてナノ医薬技術を用いて克服することで、母体への抗酸化ストレス作用を有するスタチンをHDPの治療に導入するための新規アプローチを提示することに成功した。
|
