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2023 Fiscal Year Final Research Report

The mechanism of pulmonary arteriovenous fistula in the Fontan circulation

Research Project

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Project/Area Number 21K07852
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 52050:Embryonic medicine and pediatrics-related
Research InstitutionKagoshima University

Principal Investigator

Kawamura Junpei  鹿児島大学, 医歯学域医学系, 助教 (70838656)

Co-Investigator(Kenkyū-buntansha) 上野 健太郎  鹿児島大学, 医歯学域鹿児島大学病院, 講師 (20644892)
Project Period (FY) 2021-04-01 – 2024-03-31
Keywords肺動静脈瘻
Outline of Final Research Achievements

Serum miRNAs that showed more than 2-fold higher levels in post-Glenn patients with pulmonary arteriovenous fistula (G-PAVM patients) than in other patients were selected. miR-25-3p was significantly upregulated in pulmonary artery serum in the post-Glenn group than in the other two groups (untreated cyanotic heart disease group and post-Fontan group). In vitro experiments in HMVEC-L transfected with miR-25-3p mimic showed that the expression of PHLPP2 was significantly decreased and the expression levels of HIF-1α and VEGF-A were significantly decreased after hypoxic stimulation in a PHLPP2/Akt/mTOR signaling-dependent manner increased, promoting angiogenesis, proliferation, and migration of HMVEC-L under hypoxic conditions.

Free Research Field

小児科学

Academic Significance and Societal Importance of the Research Achievements

肺動静脈瘻 (Pulmonary Arteriovenous Malformations: PAVMs) は、低酸素血症を引き起こす致死的な合併症であり、単心室症のGlenn手術後に発生したPAVMs (G-PAVMs) は深刻な問題である。本研究成果で、miR-25-3pがPHLPP2/Akt-mTORシグナルを通じて、血管内皮細胞におけるHIF-1α/VEGF-A発現を亢進させ、G-PAVMsの一因であることを証明した。miR-25-3pを制御することがG-PAVMsの治療へ発展する可能性がある。

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Published: 2025-01-30  

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