| Project/Area Number |
17K11233
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
遠藤 誠之 大阪大学, 医学系研究科, 教授 (30644794)
味村 和哉 大阪大学, 医学系研究科, 助教 (50437422)
熊澤 惠一 東京大学, 医学部附属病院, 講師 (90444546)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 妊娠高血圧症候群 / 血管内皮障害 / 補体 / PDE5阻害薬 / PLGF / 血管新生因子 / PDE阻害薬 / 補体系 / PlGF / 血管内皮 / ｓFLT1 / sFlt1 / BeWo細胞 / 産科学 |
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| Outline of Final Research Achievements |
Over the past decade, increased production of placental antiangiogenic factors has been identified as a placental factor leading to maternal endothelial dysfunction and systemic vascular dysfunctionwith respect to the pathophysiology of preeclampsia. In addition, there has been compelling evidence that complement activation is implicated in the pathogenesis of preeclampsia.First, we showed that phosphodiesterase 5 (PDE5) inhibitor, vardenafil, stimulated the production of placental growth factor (PlGF) in Bewo cell line.Second, we evaluated a possible mechanism linking the complement system to angiogenic imbalance, in which PlGF stimulated the production of complement inhibitor CFH in endothelial cell line (HUVEC), and inhibiting CFH by SiRNA making these cells vulnerable to complement activation.
Noveltherapeutic strategies aimed at restoring angiogenic and complement system imbalance is expected to ameliorate complications and prolong gestation in women with preeclampsia.
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| Academic Significance and Societal Importance of the Research Achievements |
妊娠高血圧症候群のメカニズムとしての抗血管新生状態に関する研究はすでに基礎・臨床ともに数多く存在しています。また近年、補体異常活性化の関与についての基礎的、臨床的検討の報告もなされ始めています。しかしながら、この両者、すなわち母体の抗血管新生状態と、補体の異常活性化の関連メカニズム（クロストーク）を検討した報告はほとんど見られません。一連の本研究の成果によって、両者の関連を示すメカニズムとその方法一端が明らかにすることで、抗血管新生状態と補体活性化を協調して制御することの重要性とその道筋を世界で初めて示すことになると期待しています。
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