| 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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| 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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