Therapeutic target for pulmonary hypertension based on coagulative and inflammatory cascade analysis
| Project/Area Number |
21592003
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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 | Mie University |
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Principal Investigator |
MARUYAMA Kazuo 三重大学, 大学院・医学系研究科, 教授 (20181828)
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| Co-Investigator(Kenkyū-buntansha) |
MITANI Yoshihide 三重大学, 医学部附属病院, 准教授 (60273380)
MARUYAMA Junko 鈴鹿医療科学大学, 医用工学部, 教授 (50263017)
ZHANG Erquan 三重大学, 大学院・医学系研究科, 助教 (30456727)
横地 歩 三重大学, 医学部付属病院, 講師 (60359768)
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| Project Period (FY) |
2009 – 2011
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| Project Status |
Completed (Fiscal Year 2011)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肺高血圧 / 一酸化窒素 / トロンボモジュリン / モノクロタリン |
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| Research Abstract |
The purpose of the present study was to investigate whether procoagulant state and inflammatory response occur and administration of trombomodulin(TM) prevents the development of pulmonary hypertension(PH) in monocrotaline. injected rats. Monocrotaline increased mPAP, RVH,% muscularization, and% MWT. TM treatment significantly reduced mPAP,% muscularization, and% MWT in peripheral arteries with an external diameter of 50-100μm in 19 days after monocrotaline injecton, but the effect was lost after 29 days. Monocrotaline increased the levels of tumor necrosis factor alpha, monocyte chemoattractant protein-1, and thrombin-antithrombin complex(TAT) in BALF, and expression of eNOS while peNOS was decreased. In TM-treated rats eNOS expression was decreased and peNOS was similar compared to TM-non-treated rats. A Kaplan-Meier survival curve showed no difference between rats with and without TM. Although the administration of TM might slightly delay the progression of monocrotaline-induced PH, the physiological significance for treatment is limited, since TM did not improve survival. Although exogenous TM failed to prevent the occurrence of PH in the present study, treatment to increase the endogenous production of TM in endothelial cells might reduce the severity of PH. Further investigation will be necessary.
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Report
(4 results)
Research Products
(49 results)
