Apoptosis Inhibitor of Macrophage Depletion Decreased M1 Macrophage Accumulation and the Incidence of Cardiac Rupture after Myocardial Infarction in Mice

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Title
Apoptosis Inhibitor of Macrophage Depletion Decreased M1 Macrophage Accumulation and the Incidence of Cardiac Rupture after Myocardial Infarction in Mice
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Description

Abstract
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.

(医博甲689)

Author
著者 石川 昇平
著者(ヨミ) イシカワ ショウヘイ
著者(別表記) Ishikawa Shohei
Publication Title
PLoS ONE
Publication Title Alternative
PLoS One.
Volume
12
Issue
11
Start Page
e0187894
End Page
e0187894
Publisher
Public Library of Science
Published Date
2017-11-09
ISSN
1932-6203
PMID
29121663
DOI
10.1371/journal.pone.0187894
Resource Type
Thesis or Dissertation
Language
eng
Relation
出版社版DOIリンク(URL): https://doi.org/10.1371/journal.pone.0187894
PMCID: PMC5679665
Resource URL
https://doi.org/10.1371/journal.pone.0187894
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5679665/
Rights
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.
DOI: https://doi.org/10.1371/journal.pone.0187894
Text Version
ETD
Grant ID
博甲第689号
Grant Date
2018-03-24
Degree Name
博士(医学)
Grantor
香川大学
Set
香川大学
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