Exploring the developmental process of cerebral arteriovenous malformations: an integrated analysis of in vivo angiogenesis models and clinical specimens

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17948
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56010:Neurosurgery-related
• Research Institution: Kanazawa University (2022); Akita University (2020-2021)
• Principal Investigator: Ito Yukinobu 金沢大学, 医学系, 助教 (80837732)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 動静脈奇形 / in vivo AVMモデル / 血管新生

Outline of Final Research Achievements

In this research, we focused on omics analysis of rabbit AVM models and human AVM specimens. RNA-seq analysis and small RNA-seq analysis could be performed on 2 human AVM specimens and 2 control groups. In addition, all planned analyzes were performed on the rabbit AVM specimens, and information analysis is now underway. RNA-seq analysis in the rabbit AVM model showed a tendency for fewer genes to be expressed in neovessels compared to arteries and veins. It is suggested that they have not yet differentiated into mature blood vessels. Among the genes that were found to be expressed, LGR5 was found to be expressed in all groups, and its expression was also confirmed by immunostaining of FFPE specimens.

Free Research Field

循環器病理学

Academic Significance and Societal Importance of the Research Achievements

AVMは若年から発症し、脳出血などにより脳に重い後遺障害を残す重大な疾患である。しかしながら、発症頻度の低さもあり、AVMの成因や形成過程については未だ不明な点が多い疾患である。本研究では、ヒトAVM標本に加えてウサギAVMモデルを用いることにより、AVMの新生血管に発現する遺伝子を経時的に解析することに成功した。その中でAVMの形成過程で常に発現が亢進している遺伝子をいくつか同定することができた。本研究からAVMの存在を覚知する新たなバイオマーカーの同定が期待される。また、それらをターゲットとした新規AVM治療薬の開発を目指し、AVMの早期発見、早期治療へと繋げていきたい。