Relationship between advanced glycation endproducts and chronic inflammation in diabetic vasculopathy
| Project/Area Number |
18K06861
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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 48020:Physiology-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 |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 終末糖化産物 / 血管収縮反応 / 血管弛緩反応 / 内皮機能障害 / 糖尿病 / 細胞外核酸 / 腸内細菌由来物質 / 血管機能 / 血管平滑筋 / 慢性炎症 |
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| Outline of Final Research Achievements |
Vascular dysfunction plays important roles in the initiation and development of diabetic complications. Accumulation of advanced glycation endproducts (AGEs), chronic inflammation and elevated gut-derived substances may induce vascular dysfunction. We found that augmentation of uridine dinucleotide-induced contraction and suppression of noradrenaline-induced contraction were seen in rat carotid arteries by acute and chronic AGEs exposure, respectively, TLR4 inhibitor augments endothelium-dependent relaxation in rat superior mesenteric arteries (SMAs), indoxyl sulfate impairs endothelium-dependent relaxation in aorta and SMAs via reduction of nitric oxide signaling, and trimethylamine N-oxide specifically impairs endothelium-derived hyperpolarizing factor-induced relaxation in femoral arteries but not SMAs. These results suggest that regulations of AGEs, TLRs, gut-derived substances are important strategies against diabetic vasculopathy.
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| Academic Significance and Societal Importance of the Research Achievements |
糖尿病性血管合併症は、全身で生じ得るが、様々な動脈での機能障害は未だ不明である。本研究では、様々な手法を駆使して、糖尿病時に蓄積する終末糖化産物、慢性炎症の鍵分子のトル様受容体、腸内細菌由来物質に着目し、血管機能への直接的な影響を明らかとした。さらに、血管機能重要な内皮細胞、平滑筋細胞における情報伝達機構も明らかとし、動脈部位特異的に生じる機能障害を分子レベルで解明することで、糖尿病性合併症の臓器別制御の分子基盤の一端を確立した。糖尿病は慢性疾患であり、様々な臓器機能不全からquality of life (QOL) が低下するが、本研究の成果が、QOL維持への戦略確立に繋がると確信する。
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Report
(4 results)
Research Products
(83 results)
