The impact of antisense NF-kappaB on monocrotaline-induced pulmonary hypertension in pneumonectomized mice
| Project/Area Number |
13671617
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
UEZONO Shoichi Tokyo Women's Medical University, School of Medicine, Associate Professor, 医学部, 助教授 (10291676)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAGATA Katsuyuki Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (10328461)
NOMURA Minoru Tokyo Women's Medical University, School of Medicine, Professor, 医学部, 教授 (80167577)
HOTTA Yukako Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (00318148)
KOMORI Makiko Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (60178332)
ICHIKAWA Junko Tokyo Women's Medical University, School of Medicine, Instructor, 医学部, 助手 (60318144)
原 芳樹 東京女子医科大学, 医学部, 助手 (10208663)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | pulmonary hypertension / monocrotaline / MF-KB / rat / mouse / pneumonectomy / antisense / アンチセンス |
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| Research Abstract |
The purpose of this project is to develop an animal model to produce certain pathological changes that resemble those seen in humans with primary pulmonary hypertension. Initially, this study was targeted for mice ; however, monocrotaline was found to have little effects on pulmonary vasculature. Therefore, monocrotaline was administered in pneumonectomized rats to induce proliferations of pulmonary vascular endothelial cells, which successfully lead to pulmonary arterial hypertension and pulmonary arterial neointimal formation. We then characterized physiological and pathological findings in this newly developed pulmonary hypertension model. Of note, mean pulmonary pressure rose to over 40 mmHg over three weeks following monocrotaline administration, which was markedly enhanced by nearly two-fold compared to when monocrotaline was administered alone. Using this model, rats with pulmonary hypertension were treated with antisense oligonucleotide NF-kappaB. Due to poor absorption into pulmonary vasculature when nucleotides were given intraperitoneally, this antisense failed to attenuate the development of pulmonary hypertension. Transtracheal injection of these antisense oligonucleotides is currently under investigation to maximize its therapeutic effects on pulmonary hypertension.
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Report
(3 results)
Research Products
(6 results)
