The role of Epac in the development of arteriosclerosis

• Project/Area Number: 16K08501
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General physiology
• Research Institution: Yokohama City University
• Principal Investigator: Fujita Takayuki 横浜市立大学, 医学部, 講師 (40468202)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: Epac / 動脈硬化 / EPAC / cAMP

Outline of Final Research Achievements

cAMP is one　of the most important second messengers in the body. Exchange proteins directly activated by cAMP (Epac), a novel direct effecter of cAMP, was discovered in 1998. Arteriosclerosis is an underlying cause of various important diseases, including myocardial infarction and cerebral infarction.
In this study we examined the role of Epac in the development of arteriosclerosis. There are two isoforms of Epac, Epac1 and Epac2. To examine the roles of each isoform, we generated Epac1/apolipoprotein E (Apo-E) double knockout (DKO) mice and Epac2/Apo-E DKO mice. Epac2/Apo-E DKO mice had more arteriosclerotic lesion than Apo-E single KO mice, suggesting that Epac2 may play protective roles in the development of arteriosclerosis.

Academic Significance and Societal Importance of the Research Achievements

Epacは人体の多くの組織で発現しており、血管においても内皮細胞機能や、血管平滑筋細胞の増殖や遊走などにおいて、様々な作用が報告されている。動脈硬化は多くの重要な疾患の原因である。本研究では、動脈硬化発症におけるEpacの役割を、動物モデルにおいて明らかにした。
本研究ではEpac 2が動脈硬化発症に抑制的にはたらく可能性が示唆された。心筋梗塞、脳梗塞の予防においてEpac 2が重要であることが考えられ、今後の動脈硬化による疾患の予防や治療における分子標的となりうると考えられた。