2017 Fiscal Year Final Research Report
Multiple development of treatment for pulmonary arterial hypertension by constitutive active natriuretic peptide receptor
| Project/Area Number |
15K09690
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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 |
Pediatrics
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| Research Institution | Osaka University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
高橋 邦彦 大阪大学, 医学系研究科, 招へい教員 (10610230)
那波 伸敏 大阪大学, 医学部附属病院, 医員 (30617543)
馬殿 洋樹 大阪大学, 医学部附属病院, 医員 (60644614)
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| Project Period (FY) |
2015-04-01 – 2018-03-31
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| Keywords | 小児循環器学 / 肺高血圧症 / 遺伝子治療 |
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| Outline of Final Research Achievements |
We analyzed the effect of the induction of constitutive active NPR2, which could produce massive cGMP compared to other drugs. NPR2 was induced by using Sendai-virus vectors into Sugen-Hypoxia model rat which was shown as very similar to human pulmonary hypertension. First we confirmed the safety of this treatment by immunostaining of Sendai virus, which showed no infection except for lungs. The NPR2 induction leaded significant improvement of pulmonary arterial pressure by catheter examination. In histologically, NPR2 induction demonstrated the improvement of medial wall thickness of pulmonary resistant arteries as well as the supression of small pulmonary vessel occlusion.
Next, we identified candidate small compounds, which allowed to access and stimulate guanylyl cyclase activity of NPR2 by using in silico modeling of the molecular structure of NPR2. However no small compound showed significant superior stimulative activity compared to existing drugs.
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| Free Research Field |
循環器学
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