Transcriptomic Profile of Distal Middle Cerebral Artery from Moyamoya Disease Patients Reveals a Potential Unique Pathway

Yulius Hermanto; Kent Doi; Ahmad Faried; Achmad Adam; Tondi M.  Tjili; Muhammad Z. Arifin; Yasushi  Takagi; Susumu  Miyamoto

doi:10.3889/oamjms.2020.5513

Authors

Yulius Hermanto Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan; 2Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
Kent Doi Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Ahmad Faried Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
Achmad Adam Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
Tondi M. Tjili Neurosurgery Division, Department of Surgery, Faculty of Medicine, Riau University, Pekanbaru, Indonesia
Muhammad Z. Arifin Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran, Bandung, Indonesia
Yasushi Takagi Department of Neurosurgery, Institute for Biological Sciences, Tokushima University, Tokushima, Japan
Susumu Miyamoto Department of Neurosurgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan

DOI:

https://doi.org/10.3889/oamjms.2020.5513

Keywords:

Moyamoya disease, Microarray, Middle cerebral artery, RASopathies

Abstract

BACKGROUND: Moyamoya disease (MMD) is a peculiar disease, characterized by progressive steno-occlusion of the distal ends of bilateral internal carotid arteries and their proximal branches. Numerous studies of MMD investigated as a singular pathway, thus overlooked the complexity of MMD pathobiology.

AIM: In this study, we sought to investigate the gene expression in the involved arteries to reveal the novel mechanism of MMD.

MATERIALS AND METHODS: Eight middle cerebral artery (MCA) specimens were obtained from six patients underwent surgical procedure superficial temporal artery to MCA (STA-MCA bypass) for MMD and two control patients. We performed RNA extraction and microarray analysis with Agilent Whole Human Genome DNA microarray 4x44K ver.2.0 (Agilent Tech., Inc., Wilmington, DE, USA).

RESULTS: From 42,405 gene probes assayed, 921 gene probes were differentially regulated in MCA of patients with MMD. Subsequent pathway analysis with PANTHER database revealed that angiogenesis, inflammation, integrin, platelet-derived growth factor (PDGF), and WNT pathways were distinctly regulated in MMD. Among genes in aforementioned pathways, SOS1 and AKT2 were the mostly distinctly regulated genes and closely associated with RAS pathway.

CONCLUSION: The gene expression in MCA of patients with MMD was distinctly regulated in comparison with control MCA; presumably be useful for elucidating MMD pathobiology.

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