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Published on: December 7, 2013
Identification of The Unique Subtype of Macrophages in Aneurysm Lesions at the Growth Phase
Akihiro Okada1, Hirokazu Koseki2, Isao Ono1
1Department 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.
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.
Insights
Intracranial aneurysms involve specific macrophages in lesions. These macrophages, influenced by the nervous system, represent a potential therapeutic target for this inflammatory disease.
Area of Science:
- Neuroscience
- Immunology
- Vascular Biology
Background:
- Intracranial aneurysms are characterized as macrophage-mediated inflammatory diseases of cerebral arteries.
- The specific macrophage subtypes involved in aneurysm development are not fully understood.
Purpose of the Study:
- To identify the macrophage subtype present in intracranial aneurysm lesions during the disease's growth phase.
- To investigate the potential influence of the microenvironment on macrophage differentiation in aneurysms.
Main Methods:
- Utilized a rat aneurysm model with fluorescently labeled macrophages.
- Employed laser-microdissection for macrophage isolation.
- Conducted comprehensive gene expression and gene ontology analyses.
Main Results:
- Identified a unique and monotonous macrophage subtype within aneurysm lesions.
- Gene ontology analysis highlighted nervous system signaling pathways.
- Histopathology confirmed the presence of nerves in the arterial adventitia.
Conclusions:
- The study elucidates the specific macrophage subtype in growing aneurysm lesions.
- Findings suggest a role for nervous system influence in macrophage differentiation.
- This identified macrophage subtype presents a potential therapeutic target for aneurysms.
