New paradigm for therapy for pulmonary hypertension
| Project/Area Number |
18591726
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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 | Jikei University School of Medicine |
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Principal Investigator |
UEZONO Shoichi Jikei University School of Medicine, School of Medicine, Professor (10291676)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | pulmonary hypertension / pulmonary vascular remodeling / transcription factor / Egr-1 / KLF5 / antisense / リモデリング / 核酸医薬 / アミバロテン |
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| Research Abstract |
Hypertensive pulmonary vascular disease is characterized by abnormal proliferation of vascular endothelial and smooth muscle cells, leading to pulmonary arterial hypertension (PAH), and death. Early growth response 1 (Egr-1) is a transcription factor that is rapidly activated after vascular injury, which plays an important role in vascular remodeling. We studied whether Egr-1 is a therapeutic target for PAH. o achieve effective suppression of Egr-1 in vivo, transfection with synthetic double-stranded Egr-1 decoy oligodeonucleotides was utilized in this study. Four-week-old Sprague-Dawley rats were evaluated for the development of PAH following monocrotaline (MCT, 60mg/kg) injection. Four hours prior to and just before MCT administration, either Egr-1 decoy or scrambled decoy was transfected using the hemagglutinating virus of Japan envelope vector system. Transfection of Egr-1 decoy but not scrambled decoy markedly attenuated MCT-induced PAH (mPAP=35±1 vs. 56±2, P<0.05) and vascular remodeling (VOS=0.39± 0.06 vs. 1.19±0.05, P<0.05). Egr-1 decoy may represent an effective strategy in the treatment of PAH, which provide the functional importance of Egr-1 in the MCT-induced PAH. We also investigated whether KLF 5, other transcription factor which is believed to play a pivotal role in vascular remodeling, has any impact on pulmonary vascular remodeling. Unfortunately, Am 80, a drug to suppress KLF 5 activity failed to reduce PA pressure in MCT induced PH in rats. We concluded KLF5 may not be a therapeutic target for PAH.
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Report
(3 results)
Research Products
(4 results)
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[Presentation] 周術期肺高血圧の治療2007
Author(s)
上園 晶一
Organizer
日本麻酔科学会
Place of Presentation
札幌
Year and Date
2007-05-31
Description
「研究成果報告書概要(和文)」より
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