Novel treatment for pulmonary arterial hypertension targeting endothelial mesenchymal transition.
| Project/Area Number |
25461197
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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 |
Respiratory organ internal medicine
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| Research Institution | Juntendo University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
守尾 嘉晃 順天堂大学, 医学部, 准教授 (30365663)
高橋 史行 順天堂大学, 医学部, 准教授 (70327823)
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| Project Period (FY) |
2013-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 肺高血圧症 / 血管内皮間葉転換 / 血管平滑筋 / PDGF / FGF / VEGF / 肺動脈性肺高血圧症 / 内皮間葉系転換 / Nintedanib / 血管内皮間葉系転換 / 血小板由来増殖因子 / 線維芽細胞由来増殖因子 / 血管内皮増殖因子 / 血管内皮由来増殖因子 / 慢性低酸素暴露 / SUGEN5416 |
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| Outline of Final Research Achievements |
We aimed to evaluate the usefulness of nintedanib, the triple TKI against PDGF, FGF and VEGF, as a novel treatment for pulmonary arterial hypertension (PAH) in vitro and in vivo. We, first, assessed the inhibitory effect of nintedanib on both human pulmonary arterial smooth muscle cell (HPASMC) proliferation induced by PDGF-BB and endothelial mesenchymal transition (EndMT) in human pulmonary microvascular endothelial cell (HPMVEC). Next, we tested the therapeutic effect of chronic treatment with nintedanib in PAH model rat.
Nintedanib reduced the HPASMC proliferation and expression of pERK/pAKT, and also inhibited the augmented mesenchymal marker expression in EndMT induced HPMVEC. Chronic treatment with nintedanib ameliorated the pulmonary hemodynamics and medial and intimal proliferated lesion of pulmonary arteries were decreased in PAH model rat. As a conclusion. nintedanib may be a novel treatment of PAH via inhibition of smooth muscle cell proliferation and EndMT.
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Report
(5 results)
Research Products
(3 results)
