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Sci Rep. 2019 Jul 17;9(1):10387. doi: 10.1038/s41598-019-46886-2.

RNA sequencing analysis revealed the induction of CCL3 expression in human intracranial aneurysms.

Author information

1
Innovation Center for Immunoregulation Technologies and Drugs (AK project), Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan. tomoaoki@ncvc.go.jp.
2
Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Osaka, 565-8565, Japan. tomoaoki@ncvc.go.jp.
3
Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan. tomoaoki@ncvc.go.jp.
4
Innovation Center for Immunoregulation Technologies and Drugs (AK project), Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
5
Department of Molecular Pharmacology, National Cerebral and Cardiovascular Center, Osaka, 565-8565, Japan.
6
Core Research for Evolutional Science and Technology (CREST) from Japan Agency for Medical Research and Development (AMED), Kyoto University Graduate School of Medicine, Kyoto, 606-8501, Japan.
7
Department of Neurosurgery, Tokyo Women's Medical University Medical Center East, Tokyo, 116-8567, Japan.
8
Department of Neurosurgery, Shiga University of Medical Science, Shiga, 520-2192, Japan.
9
RIKEN Preventive Medicine and Innovation Program, Saitama, 351-0198, Japan.
10
Department of Neurosurgery, Japanese Red Cross Asahikawa Hospital, Hokkaido, 070-8530, Japan.
11
Department of Neurosurgery, Tokyo Women's Medical University Yachiyo Medical Center, Chiba, 276-8524, Japan.
12
Department of Neurosurgery, Tokyo Rosai Hospital, Tokyo, 143-0013, Japan.
13
Department of Neurosurgery, Shinkawahashi Hospital, Kanagawa, 210-0013, Japan.
14
Department of Neurosurgery, NTT Medical Center Tokyo, Tokyo, 141-8625, Japan.
15
Department of Neurosurgery, Japanese Red Cross Medical Center, Tokyo, 150-8935, Japan.
16
Department of Neurological Surgery, Nippon Medical School, Tokyo, 113-8603, Japan.

Abstract

Intracranial aneurysm (IA) is a socially important disease as a major cause of subarachnoid hemorrhage. Recent experimental studies mainly using animal models have revealed a crucial role of macrophage-mediated chronic inflammatory responses in its pathogenesis. However, as findings from comprehensive analysis of unruptured human IAs are limited, factors regulating progression and rupture of IAs in humans remain unclear. Using surgically dissected human unruptured IA lesions and control arterial walls, gene expression profiles were obtained by RNA sequence analysis. RNA sequencing analysis was done with read count about 60~100 million which yielded 6~10 billion bases per sample. 79 over-expressed and 329 under-expressed genes in IA lesions were identified. Through Gene Ontology analysis, 'chemokine activity', 'defense response' and 'extracellular region' were picked up as over-represented terms which included CCL3 and CCL4 in common. Among these genes, quantitative RT-PCR analysis using another set of samples reproduced the above result. Finally, increase of CCL3 protein compared with that in control arterial walls was clarified in IA lesions. Findings of the present study again highlight importance of macrophage recruitment via CCL3 in the pathogenesis of IA progression.

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