A molecular link between vascular failure and endothelial ion channel remodeling
| Project/Area Number |
25460327
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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 |
General pharmacology
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| Research Institution | Akita University |
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Principal Investigator |
Watanabe Hiroyuki 秋田大学, 医学(系)研究科(研究院), 准教授 (80323145)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Hiroshi 秋田大学, 大学院医学系研究科, 教授 (10232464)
OOBA Takayoshi 秋田大学, 大学院医学系研究科, 助教 (80431625)
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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 |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | 受容体 / チャネル / 輸送系 / シグナル情報伝達系 / 内皮細胞 / アラキドン酸 / 血管炎症 / Oraiチャネル / 動脈硬化 / Ca 流入 / イオンチャネル / 炎症 / 血管内皮 |
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| Outline of Final Research Achievements |
Our aim was to explore the link between vascular failure and endothelial ion channel remodeling. In clinical study, we show a critical role of oxidative stress and inflammation in the development of vascular failure. In basic study, we demonstrated the constitutive expression of Orai1 and Orai3, and those co-localization in plasma membrane of cultured human coronary artery endothelial cells (hCAECs). Arachidonic acid (AA) elicited a store-independent Ca entry in hCAECs. The knockdown of either Orai-1 or Orai-3 expression drastically decreased the AA-induced Ca entry, leading to the inhibition of hCAECs proliferation. Transfection with siRNA against Orai-1 suppressed phosphorylation of cAMP-responsive element binding protein and subsequent hCAECs proliferation. These results suggest that Orai1/Orai3 is an essential component of AA-induced Ca entry pathway and is involved in hCAECs proliferation. Orai1/Orai3 might serve as a molecular link between inflammation and vascular failure.
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Report
(4 results)
Research Products
(18 results)
