Discovery of new etiologic molecules for thoracic aortic aneurysm and development of therapeutic strategies (early diagnosis / drug discovery)

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03646
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Tohoku University
• Principal Investigator: Shimokawa Hiroaki 東北大学, 医学系研究科, 客員教授 (00235681)
• Co-Investigator(Kenkyū-buntansha): 宮田 敏 帝京大学, 公私立大学の部局等, 教授 (60360343) ; 佐藤 公雄 東北大学, 高度教養教育・学生支援機構, 准教授 (80436120)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 大動脈瘤

Outline of Final Research Achievements

Thoracic aortic aneurysm (TAA) is a fatal disease that causes aortic rupture and sudden death. TAA is still a fatal disease for which there is no medical cure, and there is no proven therapeutic agent other than antihypertensive. In addition, there are still many cases in which aneurysm ruptures rapidly progress during follow-up, and there is a need for the search for new causative proteins and the development of radical therapeutic agents. We conducted a comprehensive analysis using patient-derived aortic tissue and aortic vascular smooth muscle cells, screened for novel etiological proteins, and discovered a novel etiologic molecule, SmgGDS. We found that this SmgGDS is a stretch stimulation sensor and succeeded in developing a TAA model mouse by deleting SmgGDS in vascular smooth muscle cells.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

これまでのTAA治療に関する臨床研究は、いずれも降圧薬の有効性の検証に留まってきた。かつて注目されたMarfan症候群患者におけるアンジオテンシンII受容体阻害薬による上行大動脈瘤拡大の抑制効果については、大規模比較試験により、他の降圧剤に対する優位性は否定された。従って、TAAの病因分子に着目した内科的治療薬は皆無であり、今回発見したSmgGDSに着目した治療薬開発はTAAの新しい治療法開発に繋がり、学術的・社会的意義が高いと考えられる。