Development of Nanoparticle treatment targeted NADPH oxdase in cerebral aneurysms

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16651
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Kyushu University
• Principal Investigator: Nishimura Ataru 九州大学, 大学病院, 助教 (90452755)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: NADPH oxidase / 脳動脈瘤 / 炎症

Outline of Final Research Achievements

We demonstrated by RT-PCR that rat brain microvascular endothelial cell line (GPNT) specifically expressed Nox4 among the Nox family proteins under laminar shear stress. Inflammatory molecules expressed Nox4 both under laminar and turbulent shear stress, especially, turbulent shear stress strongly increased the expression of Nox4. In experimentally induced cerebral aneurysms in rats, Nox4 were specifically expressed in cerebral aneurysms among the Nox family proteins. Immunohistochemistry demonstrated that the expression of Nox4 was high in the neck of aneurysms where turbulent shear stress loads. We examined the roles of Nox4 in GPNT by Nox4 overexpression using virus vector. Nox4 overexpression downregulated the expression of MCP-1, an Inflammatory molecules which is upregulated both in laminar and turbulent shear stress, The upregulated Nox4 may control the expression of MCP-1 in endothelial cell, thereby restraining the enlargement of cerebral aneurysms.

Free Research Field

脳血管障害

Academic Significance and Societal Importance of the Research Achievements

本研究でNox4は脳動脈瘤において、炎症の強く起こる乱流部に発現し、動脈瘤の形成・増大に強く関わるMCP1の発現を抑制 することで保護的な役割を担っていることが示唆された。今後は内皮に発現するNox4をターゲットとした脳動脈瘤の形成・増大を抑制するための新規薬剤の開発が期待される。