2016 Fiscal Year Final Research Report
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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| Project Period (FY) |
2013-04-01 – 2017-03-31
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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 |
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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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| Free Research Field |
肺高血圧・肺循環障害
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