2021 Fiscal Year Final Research Report
Elucidation of the cardiovascular network mechanism mediated by senescent vascular endothelial cell-derived factors
| Project/Area Number |
19K11759
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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 59040:Nutrition science and health science-related
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| Research Institution | Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology |
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Principal Investigator |
Sasaki Norihiko 地方独立行政法人東京都健康長寿医療センター(東京都健康長寿医療センター研究所), 東京都健康長寿医療センター研究所, 研究員 (80639063)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 内皮細胞 / 細胞老化 / へパラン硫酸脱硫酸化酵素 / 平滑筋細胞 / 形質転換 / ガングリオシド |
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| Outline of Final Research Achievements |
It was found that heparan sulfate desulfurizing enzyme 2 is not involved in the induction of cellular senescence. From in vivo analysis, it was found that heparan sulfate desulfurizing enzyme 2 is highly expressed in the aortic vascular endothelium of aged mice and the vascular endothelium of the heart, and is also increased in blood levels in aged mice. In order to proceed with in vivo analysis, we proceeded with the creation of vascular endothelium-specific knockout mice of heparan sulfate desulfurizing enzyme 2. Furthermore, it was found that the proportion of the main component of gangliosides, which is a group of glycolipids, increases during dedifferentiation in vascular smooth muscle cells, on which heparan sulfate desulfurizing enzyme 2 may act.
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| Free Research Field |
糖鎖生物学、老化研究、血管生物学
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| Academic Significance and Societal Importance of the Research Achievements |
生活習慣病の増加する中年層から高齢層にかけて生体内では老化細胞が蓄積し、動脈硬化を発端とする心血管疾患の発症、進展につながると考えられているが、詳しい分子メカニズムは不明である。今回の成果では、へパラン硫酸脱硫酸化酵素2がヒトの培養血管内皮細胞のみならず、マウス生体の加齢に伴って心血管および血中で増加すること、さらに血管の恒常性維持に働く平滑筋細胞の機能を制御する可能性が示された。今後さらにin vitroおよびin vivo研究をすすめることにより、へパラン硫酸脱硫酸化酵素2を標的とした心血管疾患を含む加齢性疾患の新たな治療法や予防法の開発につながると期待される。
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