Role of aging regulatory protein WRN in cardiac fibrosis
| Project/Area Number |
16K09496
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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 | Nagoya University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
吉田 恭子 (今中恭子) 三重大学, 医学系研究科, 准教授 (00242967)
室原 豊明 名古屋大学, 医学系研究科, 教授 (90299503)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | ウェルナー症候群 / 心臓拡張不全 / 心不全 / オートファジー / 酸化ストレス / 老化 / 線維化 / 循環器・高血圧 / 糖尿病 |
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| Outline of Final Research Achievements |
[Background/Introduction] Aging is known to be one of the primary causes of heart failure. Werner syndrome is one of the aging disorder that caused by dysfunction of DNA helicase-regulatory protein (WRN). [Results] WRN-K577M exhibited diffuse left-ventricular (LV) hypertrophy, enhanced fibrosis, and diastolic LV
dysfunction with preserved systolic ejection fraction. DNA microarray analysis of WRN-K577M heart revealed that the 253 genes were upregulated including hypertrophy, fibrosis, inflammation, and oxidative stress. Notably, p62 and LC3-II/I were increased in myocardium of WRN-K577M. Blockade of the lysosomal fusion into autophagosome by systemic treatment with chloroquine reduced LC3-II/I ratio.[Conclusion(s)] In WRN-mutant progeria model, off-rate disorder of cardiac autophagy is, at least in part, the cause of increase in oxidative stress and inflammation in heart leading to HFpEF.
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢化社会に突入し、高齢者心不全患者数の増加とその予防は喫緊の課題である。本研究の成果は、高齢者に最も多いと言われる拡張不全型心不全の予防介入として、オートファジー活性調整が有用である可能性を示唆している。
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Report
(4 results)
Research Products
(8 results)
