Identification of the unique subtype of macrophages in aneurysm lesions at the growth phase

Abstract Background Considered with the devastating outcome of subarachnoid hemorrhage due to rupture of intracranial aneurysm (IA), a novel therapeutic strategy based on the pathogenesis of IAs should be established. Recent experimental studies have defined IAs 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 or contributes to the pathogenesis remains to be elucidated. Methods The previously-established aneurysm model of rats were used. Macrophages were labeled with the fluorescent protein, DiI, and labelled cells were 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. The gene expression profile data from in vitro-differentiated bone marrow derived macrophages was acquired from the database and used as a reference data. The histopathological examinations to validate the results were also done. Results The gene expression profile data of total 52 macrophages infiltrating into the lesions was acquired. The principal component analysis failed to form multiple cluster, suggesting that macrophages infiltrating in the lesions were monotonous. By comparing the profile of the macrophage subtype identified with one from in vitro-differentiated M0 or M1 macrophages, the macrophages in the lesions were found to be belonged to the simple and unique subtype. Because the perception of signaling from nervous system was highlighted as terms up-represented compared with terms in M0 or M1 macrophages through gene ontology analyses, the macrophage subtype in the aneurysm lesions at the growth phase might be differentiated under the influence of nervous system in the microenvironment of the disease. The histopathological examinations clarified the presence of nerves in the adventitia of intracranial artery bifurcation, supporting the above notion. 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 this subtype or genes specifically expressed in this subtype as a therapeutic target.