Contribution of vascular smooth muscle cells and inflammation to the development of occlusive pulmonary vascular disease
| Project/Area Number |
18K07841
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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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| Review Section |
Basic Section 52050:Embryonic medicine and pediatrics-related
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| Research Institution | Mie University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
丸山 一男 三重大学, 医学系研究科, 教授 (20181828)
澤田 博文 三重大学, 医学系研究科, 講師 (30362354)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 肺高血圧 / 動物モデル / ゲノム編集 / 炎症 / CCR2 / ケモカイン / MCP1 / ノックアウトラット / 肺動脈性肺高血圧 / 血管平滑筋 |
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| Outline of Final Research Achievements |
Using genome-edited rats, we determined the origin of intimal smooth muscle cells in pulmonary vascular lesions of PAH and elucidated whether CCR2 is essential for the formation of intimal lesions in PAH in vivo.(A) Effect of PAH on pulmonary vascular lesions in CCR2 knock-out rats: Hemodynamics was evaluated by echocardiography and cardiac catheterization, and hemodynamic and tissue lesions were improved in knock-out rats. (B) Fate mapping analysis of differentiated smooth muscle cells in a PAH model using Myh11-Cre rats: We have now succeeded in generating Myh11-Cre-ERT2 knock-in rats using genome editing technology.
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| Academic Significance and Societal Importance of the Research Achievements |
CCR2を介した炎症がラット肺高血圧の肺血管病変の発症、進展に必須であることが判明した。これにより、肺高血圧の病変形成の機序の解明における、CCR2を介した経路の解明につながる。さらに、CCR2ないしその下流の重要な経路を標的とする分子標的治療の可能性を開く。さらに肺高血圧の閉塞性肺血管病変の血管平滑筋由来の細胞の関与が明らかになれば、その分化、遊走が内膜肥厚の形成に繋がるか否かの検討が初めて可能となる。それを踏まえて、内膜形成における分子標的治療の開発への可能性が広がる。
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Report
(2 results)
Research Products
(8 results)
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[Journal Article] Prediction of Pulmonary to Systemic Flow Ratio in Patients With Congenital Heart Disease Using Deep Learning-Based Analysis of Chest Radiographs2020
Author(s)
Shuhei Toba, MD; Yoshihide Mitani, MD, PhD; Noriko Yodoya, MD; Hiroyuki Ohashi, MD; Hirofumi Sawada, MD, PhD; Hidetoshi Hayakawa,MD, PhD; Masahiro Hirayama, MD, PhD; Ayano Futsuki, MD; Naoki Yamamoto, MD; Hisato Ito,MD, PhD; Takeshi Konuma, MD, PhD; Hideto Shimpo,MD, PhD; Motoshi Takao, MD, PhD
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Journal Title
JAMA Cardiology
Volume: -
Issue: 4
Pages: 449-457
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] A non-selective endothelin receptor antagonist bosentan modulates kinetics of bone marrow-derived cells in ameliorating pulmonary hypertension in mice.2020
Author(s)
Kato T, Mitani Y, Masuya M, Maruyama J, Sawada H, Ohashi H, Ikeyama Y, Otsuki S, Yodoya N, Shinohara T, Miyata E, Zhang E, Katayama N, Shimpo H, Maruyama K, Komada Y, Hirayama M.
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Journal Title
Pulm Circ.
Volume: 10
Issue: 2
Pages: 1-9
DOI
Related Report
Peer Reviewed / Open Access
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