| Project/Area Number |
25461100
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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 |
Cardiovascular medicine
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| Research Institution | Kurume University (2014-2015)
Tohoku University (2013) |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
Shimokawa Hiroaki 東北大学, 大学院医学系研究科, 教授 (00235681)
Satoh Kimio 東北大学, 学内共同利用施設等, 准教授 (80436120)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 右心不全 / 右室線維化 / Rhoキナーゼ / 内皮型一酸化合成酵素 / コラーゲン代謝 / 内皮型一酸化窒素合成酵素 |
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| Outline of Final Research Achievements |
Pulmonary hypertension (PH) finally causes right ventricular (RV) failure. We examined the mechanisms of RV remodeling in PH.
In human RV autopsy samples, RV failure was associated with RV hypertrophy, interstitial and perivascular fibrosis, decreased capillary density and increased macrophage recruitment. Further, perivascular MMP2 and Rho-kinase activity were increased in PH patients. In animals, both hypoxic ndothelial nitric oxide synthase-deficient (eNOS-/-) and collagenase-resistant knock-in (ColR/R) mice developed greater extent of RV hypertrophy, perivascular remodeling and macrophage infiltration compared with WT mice. ColR/R mice were able to increase their capillary density in the RV in response to hypoxia. Both mouse models showed increased Rho-kinase activation.
RV remodeling occurs early during PH development through fibrosis, perivascular remodeling, and capillary rarefaction, in which eNOS pathway and collagen metabolism can be new therapeutic targets.
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