| Project/Area Number |
18K15967
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
Ohta-Ogo Keiko 国立研究開発法人国立循環器病研究センター, 病院, 医長 (30601827)
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| Project Period (FY) |
2018-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2020: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | pulmonary hypertension / collagen disease / inflammation / T-lymphocyte / macrophages / immunohistochemistry / 炎症細胞 / Tリンパ球 / 肺高血圧 / 膠原病 / 炎症 / 右心不全 / 肺高血圧症 / 循環器病理学 / 組織リモデリング |
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| Outline of Final Research Achievements |
In this study, autopsy cases were pathologically evaluated to clarify the inflammatory microenvironment in the lung tissue of pulmonary arterial hypertension associated with connective tissue disease (CTD-PAH). Histologically, the lesions in the lung tissues of patients other than systemic sclerosis were basically similar to those of idiopathic PAH and were often accompanied by pulmonary vein lesions, while systemic sclerosis typically had a pulmonary veno-occlusive disease (PVOD)-like morphology. Inflammation of the pulmonary veins as well as the pulmonary arteries was a characteristic feature of CTD-PAH. On the other hand, T lymphocyte and macrophage types in the inflammatory zone were similar between the CTD-PAH and idiopathic PAH or PVOD. The inflammatory microenvironment was implicated as a common contributor in the development of the conditions, based on the characteristics of helper T cells, cytotoxic T cells, M2 macrophages, proinflammatory cytokines, and chemokine receptors.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究において得られた、膠原病に伴う肺動脈性肺高血圧症が、組織学的に強皮症と強皮症以外でやや異なる形態をとること、しかし、いずれも肺動脈のみならず肺静脈の炎症も伴うことに特徴付けられるのは治療を考慮する上で重要なポイントである。今回確認された免疫担当細胞の特徴から想定される炎症性微小環境は、膠原病に伴う肺動脈性肺高血圧症に特異的なわけではなく、特発性肺動脈性肺高血圧症および肺静脈閉塞症とも共通したものであり、炎症をターゲットとした新規薬物治療に向けたヒトにおける基礎となる知見として意義があると考えられる。
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