Exploration for Aggravating Process of Heart Failure Induced by Specific Interaction with G-protein-coupled Receptor and Toll-like Receptor
| Project/Area Number |
25461108
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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 | Osaka University |
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Principal Investigator |
Sanada Shoji 大阪大学, 医学(系)研究科(研究院), 招へい教員 (70593797)
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| Co-Investigator(Kenkyū-buntansha) |
MINAMINO Tetsuo 大阪大学, 大学院医学系研究科, 准教授 (30379234)
HIGO Shuichiro 大阪大学, 大学院医学系研究科, 助教 (00604034)
ASANO Yoshihiro 大阪大学, 大学院医学系研究科, 助教 (60527670)
TSUKAMOTO Osamu 大阪大学, 大学院医学系研究科, 助教 (80589151)
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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: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 慢性心不全 / 自然免疫 / 心筋保護 / 心不全 / 内因性免疫 / G蛋白共役受容体 / 心筋リモデリング / 心筋細胞 / G蛋白共役性受容体 / IL-33 / ST2受容体 / MAPキナーゼ / NF-kB / 心筋肥大 / アポトーシス |
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| Outline of Final Research Achievements |
We and others have reported that ablation of ST2 caused exaggerated cardiac remodeling in both ischemic and non-ischemic HF. We tested whether IL-33 protects myocardium against HF induced by mechanical overload. Following TAC, myocardial mRNA expressions of Th2 cytokines were diminished while those of Th1 were enhanced in IL-33KO mice than in WT mice. After 8-weeks, IL-33KO mice exhibited exacerbated LV hypertrophy, increased chamber dilation, reduced fractional shortening, aggravated fibrosis and impaired survival compared with WT littermates. Accordingly, myocardial mRNA expressions of fibrogenic (TGF-b1/Collagen3a1) as well as hypertrophic (c-Myc/BNP) molecular markers were also significantly enhanced in IL-33KO mice than those in WT mice. In conclusion, the ablation of IL-33 directly and significantly lead to exacerbate cardiac remodeling with impaired cardiac function and survival upon mechanical stress. These data reveal a potential therapeutic role for IL-33 in non-ischemic HF.
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Report
(4 results)
Research Products
(4 results)
