administration of M2 macrophages suppresses expansion of aortic aneurysms in mice

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K16384
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Nagoya University
• Principal Investigator: OGATA Aika 名古屋大学, 医学系研究科, 特任講師 (70718311)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: 大動脈瘤 / 炎症 / マクロファージ / 形質転換

Outline of Final Research Achievements

Aortic aneurysm (AA) is a serious and life-threatening disease. Although significant advances have been made in open surgery and endovascular repair, no medical therapies are available to prevent AA growth. Appearance of many M1MF is observed along with secretion of proinflammatory cytokines and chemokines in AA progression. Equal proportions of M1/M2 leads to aneurysm stability, whereas increased population of M1MF predisposes the aneurysm to rupture. We hypothesized that inducing the high dominant localization of M2MF at the lesion site of AA and regulating the M1/M2 ratio might be a therapeutic strategy of AA treatment.
M1MF had significantly decreased gene expressions by M2MF co-culture. M2MF exhibited significant decrease MMP-9 compared with AA tissue mono-culture. Administration of M2MF inhibited AA expansion through the improvement of inflammatory reaction with the dominance of M2MF. This study provides that M2MF administration might be useful for the treatment of AA.

Free Research Field

心臓血管、再生医療

Academic Significance and Societal Importance of the Research Achievements

高齢化や生活習慣病人口の増加に伴い、大動脈瘤罹患患者数は増加している。大動脈瘤は、大動脈が瘤のように膨らむ疾患で、動脈硬化が主な原因となる。瘤は自然に退縮することはなく、破裂した場合は生命に危険が及ぶ。標準治療である人工血管置換術は、破裂予防効果は絶大だが、手術侵襲が大きい。また、手術対象患者は高齢化しており、ハイリスク症例では術後合併症などを考慮すると、手術を躊躇することも少なくない。従って、超低侵襲な大動脈瘤治療法の開発は国民的課題である。本研究成果は、臨床的意義を考慮すれば超低侵襲な大動脈瘤治療法への布石となり得る。