Clarification of ERK5-mediated endothelial mesenchymal transition suppression mechanism and its application to the prevention of arteriosclerosis

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08549
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General pharmacology
• Research Institution: The University of Tokushima
• Principal Investigator: IZAWA-ISHIZAWA Yuki 徳島大学, AWAサポートセンター, 准教授 (40610192)
• Co-Investigator(Kenkyū-buntansha): 池田 康将 徳島大学, 大学院医歯薬学研究部(医学域), 准教授 (60432754) ; 今西 正樹 徳島大学, 病院, 助教 (00734344)
• Research Collaborator: ABE Jun-ichi
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 内皮間葉転換 / 動脈硬化 / ERK5 / 血管内皮細胞

Outline of Final Research Achievements

A study was conducted to clarify the involvement of ERK5 activation and endothelial mesenchymal transition (EndMT) in the arteriosclerosis-related diseases. Statins and quercetin, a kind of polyphenol, increased the expression of nitric oxide synthase (NOS) through ERK5 activation in cultured vascular endothelial cells. It was revealed that VE-cadherin expression, which is an endothelial cell marker involved in EndMT, is also increased in accordance with the increase or decrease of NOS expression. The vascular endothelial cell protective effect of these drugs was also confirmed from the improvement of the vascular injury caused by nitric oxide synthase inhibitor administration in mice. From the above, it is suggested that ERK5 activation may contribute to the prevention of the onset of the arteriosclerosis-related diseases.

Free Research Field

循環薬理学

Academic Significance and Societal Importance of the Research Achievements

粥状動脈硬化や大動脈瘤、大動脈解離、虚血性心疾患、脳卒中など、高血圧や加齢などを基礎疾患とする動脈硬化性疾患は、今なお日本人の主な死亡原因を占めているのが現状である。動脈硬化巣の形成は慢性的に進行するが、それに伴っておこる心血管イベントは予兆なく急激に発症し、致死的な転機をたどることも少なくない。そのため、イベント発症機序を明らかにし、予防戦略を確立することは非常に社会的意義がある。本研究課題では内皮間葉転換に着目し、内皮細胞におけるERK5活性化が動脈硬化性疾患のイベント発症予防に貢献し得る可能性を見出した。