The molecular mechanisms underlying release and signaling of extracellular vesicles in the vascular dysfunction of metabolic disorder
| Project/Area Number |
18K06974
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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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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Hoshi University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | 細胞外小胞 / 血管障害 / 代謝性疾患 / 糖尿病 / 血管内皮細胞機能 / マイクロパーテイクル / 血管機能 |
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| Outline of Final Research Achievements |
Extracellular vesicles(EVs) have been described as biological vectors of vascular diseases in other pathologies. I found that 1) indoxyl sulfate, Advanced Glycation End Products, and UTP directly affects vascular function, especially, endothelium-dependent vasorelaxation ;2) GLP-1 causes vascular relaxation in diabetic aorta through GLP-1-dependent beta-arrestin2 recruitment ;3)extracellular signal-regulated kinases (ERK)1/2 accumulated more in diabetic EVs than in control mice-derived EVs;4) diabetic EVs induced ERK1/2 activation in mice aortas;5) in vivo treatment with ERK-inhibitor ameliorates vascular endothelial dysfunction in diabetic mice. I propose that ERK-inhibitor may be a promising therapeutic agent for EV derived-cardiovascular complications in metabolic disorder.
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| Academic Significance and Societal Importance of the Research Achievements |
動脈硬化、脳梗塞、心筋梗塞等の血管障害は、様々な代謝性機能不全の重積による合併症であり、患者の quality of life (QOL) を著しく低下する。近年、細胞外小胞 (Extracellular vesicles: EVs) は、その血液を循環する特性や、重要な生理機能が注目されており、この機能解明と血管障害との関係を明らかにすることは、革新的な新規治療薬開発につながる。本研究により、代謝性疾患時における血管障害において、EVの阻害、EVに関するシグナル伝達の阻害は、新たな血管障害の改善アプローチに繋がることを明らかにした。
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Report
(4 results)
Research Products
(84 results)
