| Project/Area Number |
17K09597
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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 |
Cardiovascular medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Makoto Okazawa 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (40414130)
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| Co-Investigator(Kenkyū-buntansha) |
中岡 良和 国立研究開発法人国立循環器病研究センター, 研究所, 部長 (90393214)
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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 |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肺高血圧症 / TrkB / 循環器・高血圧 / 免疫学 |
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| Outline of Final Research Achievements |
Pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, leading to right ventricular overload, hypertrophy, and dilatation. Neurotrophic tyrosine receptor kinase type 2 (TrkB) regulates various physiological and pathological processes. However, the role of TrkB signaling in the pathological processes of PAH is not well understood. Brain-derived neurotrophic factor (BDNF)-TrkB signaling activated inflammatory signals in lung organ culture and air-liquid interface culture of bronchial epithelial cells. Conditional TrkB knockout mice showed increased Fulton’s index, increased RV fibrosis, and reduced RVEF after 4-week hypoxia exposure. BDNF-TrkB signaling might have a protective role in right ventricular remodeling in PAH.
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| Academic Significance and Societal Importance of the Research Achievements |
PAH病態が進行すると、右心室に負荷がかかることで心臓の働きが悪くなり、右心不全を引き起こす。右心不全は、PAHの重要な予後規定因子であり、慢性右心不全に対しては、血液循環の悪化による水分貯留に対する利尿薬による対症療法がなされる。本研究で得られた、BDNF-TrkBシグナルが低酸素誘発性肺高血圧症モデルマウスにおける右心室負荷に対する保護作用を有するとの結果は、PAHにおける右心不全に対する新規治療ターゲットとなる可能性を示唆する。
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