A molecular link between vascular failure and endothelial ion channel remodeling

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460327
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: Akita University
• Principal Investigator: Watanabe Hiroyuki 秋田大学, 医学(系)研究科(研究院), 准教授 (80323145)
• 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)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: 受容体 / チャネル / 輸送系 / シグナル情報伝達系

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.

Free Research Field

医歯薬学