Elucidation of molecular mechanism of moyamoya disease for prophylaxis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25893104
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Hygiene and public health
• Research Institution: Kyoto University
• Principal Investigator: KOBAYASHI Hatasu 京都大学, 医学(系)研究科(研究院), 講師 (70542091)
• Project Period (FY): 2013-08-30 – 2015-03-31
• Keywords: もやもや病 / RNF213 / iPS細胞 / 血管内皮細胞 / 動物モデル

Outline of Final Research Achievements

Moyamoya disease (MMD) is a cerebrovascular disease characterized by occlusive lesions in the circle of Willis. The Mysterin (RNF213) R4810K polymorphism increases susceptibility to MMD. Mysterin R4810K reduced angiogenic activities of induced pluripotent stem cell-derived vascular endothelial cells (iPSECs) from patients with MMD. Overexpression of Mysterin R4810K inhibited angiogenic activity of human umbilical vein endothelial cells, while overexpression of Mysterin wild type (WT) did not. In addition, Mysterin R4810K was demonstrated to induce mitotic abnormalities and increased risk of genomic instability. To confirm the anti-angiogenic effect of Mysterin upregulation in vivo, vascular endothelial cell- or smooth muscle cell-specific Mysterin R4757K (R4810K orthologue) or WT transgenic mice were exposed to hypoxia. Cerebral angiogenesis by hypoxia was suppressed in endothelial cell-specific Mysterin R4757K transgenic mice, while it was not suppressed in other mice.

Free Research Field

予防医学