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Identification of The Unique Subtype of Macrophages in Aneurysm Lesions at the Growth Phase

  • Akihiro Okada
    Affiliations
    Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan

    Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan

    Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
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  • Hirokazu Koseki
    Affiliations
    Department of Neurosurgery, The Jikei University School of Medicine, Tokyo, Japan
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  • Isao Ono
    Affiliations
    Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan

    Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan

    Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
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  • Tomomichi Kayahara
    Affiliations
    Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan

    Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan

    Department of Cerebrovascular Surgery, Saitama Medical University International Medical Center, Saitama, Japan
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  • Hiroki Kurita
    Affiliations
    Department of Cerebrovascular Surgery, Saitama Medical University International Medical Center, Saitama, Japan
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  • Susumu Miyamoto
    Affiliations
    Department of Neurosurgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
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  • Hiroharu Kataoka
    Affiliations
    Department of Neurosurgery, National Cerebral and Cardiovascular Center, Osaka, Japan
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  • Tomohiro Aoki
    Correspondence
    Corresponding author at: Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, 6-1 Kishibe-Shinmachi, Suita City, Osaka 564-8565, Japan.
    Affiliations
    Department of Molecular Pharmacology, Research Institute, National Cerebral and Cardiovascular Center, Osaka, Japan

    Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), National Cerebral and Cardiovascular Center, Osaka, Japan
    Search for articles by this author

      Abstract

      Objectives

      Recent experimental studies have defined intracranial aneurysms as a macrophage-mediated chronic inflammatory disease affecting intracranial arteries. Although there are various subtypes in macrophages, what type of macrophages is present in lesions during the disease development remains to be elucidated.

      Methods

      The previously-established aneurysm model of rats was used. Macrophages were labeled with the fluorescent protein and isolated by a laser-microdissection method. The comprehensive gene expression profile analyses and gene ontology analyses was then done to identify a macrophage subtype present in lesions at the growth phase.

      Results

      The gene expression profile data of total 52 macrophages infiltrating into the lesions was acquired. The principal component analysis revealed the monotonous macrophage subtype. By comparing the profile identified with one from in vitro-differentiated M0 or M1 macrophages, the macrophages in the lesions were belonged to the simple and unique subtype. Because the perception of signaling from nervous system was highlighted as up-represented terms through gene ontology analyses, the macrophage subtype in lesions at the growth phase might be differentiated under the influence of nervous system in the microenvironment. The histopathological examinations supported the above notion by confirming the presence of nerves in the adventitia.

      Conclusions

      The findings from the present study have provided the useful insights about the macrophage subtype in aneurysm lesions at the growth phase and also proposed its ability as a therapeutic target.

      Key Words

      Abbreviations:

      CCA (common carotid artery), GO (gene ontology), IA (intracranial aneurysm), SAH (subarachnoid hemorrhage)
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