Involvement of complement activation in the pathogenesis of gestational hypertension syndrome -Crosstalk between complement system and angiogenesis-

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09618
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Osaka University
• Principal Investigator: Tomimatsu Takuji 大阪大学, 大学院医学系研究科, 招へい教授 (30346209)
• Co-Investigator(Kenkyū-buntansha): 味村 和哉 大阪大学, 大学院医学系研究科, 助教 (50437422)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 妊娠高血圧症候群 / 血管内皮障害 / 補体 / 補体制御タンパク / 抗血管新生因子

Outline of Final Research Achievements

The underlying mechanism of preeclampsia by which an angiogenic imbalance results in systemic vascular endothelial dysfunction remains unclear. Complement activation directly induces endothelial dysfunction and is known to be involved in preeclampsia; nevertheless, the association between complement activation and angiogenic imbalance has not been established. This research aimed to evaluate whether angiogenic imbalance affects the expression and secretion of inhibitory complements in various cell types including endothelial cells.
An angiogenic imbalance, including decreased PlGF and increased sFlt1, suppresses CFH expression and secretion, resulting in complement activation on the surface of endothelial cells and systemic vascular endothelial dysfunction. In addition, these angiogenic imbalances affect the expression of various inhibitory proteins in different cell types.

Free Research Field

周産期

Academic Significance and Societal Importance of the Research Achievements

本研究により、HDPの際の母体の抗血管新生状態による補体の異常活性化のプロセスの一部ではあるが明らかになったことにより、近年開発された薬剤による補体抑制治療による、副作用に配慮した疾患特異的な補体抑制治療の実用化への布石となったと考える。