2026-03-11T11:01:06Z https://kagawa-u.repo.nii.ac.jp/oai

oai:kagawa-u.repo.nii.ac.jp:00000309 2024-10-31T08:02:34Z 13:40

Apoptosis inhibitor of macrophage depletion decreased M1 macrophage accumulation and the incidence of cardiac rupture after myocardial infarction in mice Ishikawa, Shohei 石川, 昇平 イシカワ, ショウヘイ open access Copyright: © 2017 Ishikawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. This research was supported by a Core Research for Evolutional Medical Science and Technology grant funded by the Agency for Medical Research and Development (AMED-CREST) (to Akira Nishiyama) and Grants‐in‐aid from the Ministry of Education, Culture, Sports, Science and Technology, Japan (to Tetsuo Minamino). Background Cardiac rupture is an important cause of death in the acute phase after myocardial infarction (MI). Macrophages play a pivotal role in cardiac remodeling after MI. Apoptosis inhibitor of macrophage (AIM) is secreted specifically by macrophages and contributes to macrophage accumulation in inflamed tissue by maintaining survival and recruiting macrophages. In this study, we evaluated the role of AIM in macrophage accumulation in the infarcted myocardium and cardiac rupture after MI. Methods and results Wild-type (WT) and AIM‒/‒ mice underwent permanent left coronary artery ligation and were followed-up for 7 days. Macrophage accumulation and phenotypes (M1 pro-inflammatory macrophage or M2 anti-inflammatory macrophage) were evaluated by immunohistological analysis and RT-PCR. Matrix metalloproteinase (MMP) activity levels were measured by gelatin zymography. The survival rate was significantly higher (81.1% vs. 48.2%, P<0.05), and the cardiac rupture rate was significantly lower in AIM‒/‒ mice than in WT mice (10.8% vs. 31.5%, P<0.05). The number of M1 macrophages and the expression levels of M1 markers (iNOS and IL-6) in the infarcted myocardium were significantly lower in AIM‒/‒ mice than in WT mice. In contrast, there was no difference in the number of M2 macrophages and the expression of M2 markers (Arg-1, CD206 and TGF-β1) between the two groups. The ratio of apoptotic macrophages in the total macrophages was significantly higher in AIM‒/‒ mice than in WT mice, although MCP-1 expression did not differ between the two groups. MMP-2 and 9 activity levels in the infarcted myocardium were significantly lower in AIM‒/‒ mice than in WT mice. Conclusions These findings suggest that AIM depletion decreases the levels of M1 macrophages, which are a potent source of MMP-2 and 9, in the infarcted myocardium in the acute phase after MI by promoting macrophage apoptosis, and leads to a decrease in the incidence of cardiac rupture and improvements in survival rates. eng doctoral thesis P https://kagawa-u.repo.nii.ac.jp/records/309 https://doi.org/10.1371/journal.pone.0187894 https://dl.ndl.go.jp/pid/11122658 http://www.ncbi.nlm.nih.gov/pmc/articles/pmc5679665/ 29121663 500001069925 甲第689号 博士（医学） 2018-03-24 16201 香川大学 Kagawa University https://kagawa-u.repo.nii.ac.jp/record/309/files/Med_A689.pdf application/pdf 5.6 MB 2020-10-30 https://kagawa-u.repo.nii.ac.jp/record/309/files/Med_A689_abstract.pdf application/pdf 85.8 kB 2020-10-30 https://kagawa-u.repo.nii.ac.jp/record/309/files/Med_A689_result.pdf application/pdf 354.3 kB 2020-10-30