Development of a novel therapy targeting the interaction between mechanical stress and immune-inflammatory responses

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19583
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Yamaguchi University
• Principal Investigator: YOSHIMURA Koichi 山口大学, 大学院医学系研究科, 准教授(特命) (00322248)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: 大動脈瘤 / 大動脈解離 / 力学刺激

Outline of Final Research Achievements

Aortic aneurysm and aortic dissection are life-threatening diseases due to aortic rupture. Since therapeutic options are limited, development of novel pharmacotherapy has been needed. In this study, we found that inordinate level of mechanical stress on macrophages accelerated immune-inflammatory responses. Further, isoform-specific inhibition of c-Jun N-ternimal kinase（JNK）reduced inflammatory responses in macrophages and also slowed disease progression, under mechanical stress conditions.

Free Research Field

心臓血管外科学

Academic Significance and Societal Importance of the Research Achievements

本研究における発見から、大動脈瘤・大動脈解離の病変部特有の力学刺激と免疫・炎症応答系との連関が制御可能であることと、その制御が新規治療法に繋がる可能性があることが示された。病変部特有の力学刺激と免疫・炎症応答系との連関を標的とすれば、全身の免疫系には影響しない、副作用の少ない治療法が期待できる。広く慢性炎症性疾患に対する新たな作用機序の抗炎症薬の提供にも繋がる。