Elucidation of Vascular Remodeling through the Senescence Signal in Aortic Diseases

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K10653
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Niigata University
• Principal Investigator: nagasawa ayako 新潟大学, 医歯学総合病院, 助教 (20768999)
• Co-Investigator(Kenkyū-buntansha): 清水 逸平 新潟大学, 医歯学総合研究科, 特任准教授 (60444056) ; 土田 正則 新潟大学, 医歯学系, 教授 (60293221) ; 南野 徹 新潟大学, 医歯学系, 教授 (90328063)
• Research Collaborator: Okuda Shujiroh ; Soga Tomoyoshi ; Aoki Junken ; Hayano Toshiya ; Sakimura Kenji ; Sasaoka Toshikuni
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 大動脈疾患 / 細胞老化

Outline of Final Research Achievements

The purpose of this study is to elucidate role of senescence cell in aortic diseases, dissection and aneurysm. In C57BL6/NCr mice, AngII infusion led to marked increase in p53 signal both in smooth muscle cells. To further test the role of p53-induced cellular senescence in aortic dissection, we generated transgenic models by genetically manipulating p53 with cre-lox system. We generated smooth muscle specific p53 gain (SMC-p53 O/E) or knockout models (SMC-p53 KO). Both models were subjected to high dose AngII (AngII; 2500ng/kg/min), and we found incidence of aortic dissection was more predominant in SMC-p53 KO mice compared to SMC-p53 O/E model. Aortic dissection develops when blood leaks through a tear in the inner layer of aorta. It is widely known that senescent cells become resistant for apoptosis. Our data indicates that cellular senescence in vascular cells has protective roles for the suppression of aortic dissection possibly by mediating an anti-apoptotic effect.

Free Research Field

心臓血管外科

Academic Significance and Societal Importance of the Research Achievements

大動脈瘤は血圧管理を主体とするリスク管理以外、瘤の拡大抑制に向けた直接的な医療介入ができず、大動脈解離の発症は事前に察知することが不可能である点が医療上問題である。大動脈瘤や急性大動脈解離といった大血管疾患が細胞老化を介して発症、進展するという仮説を検証するのが本研究の特色、かつ独創的な点である。本研究を遂行することで、これらの大動脈疾患に対し、細胞老化制御を介した全く新しい疾患概念や治療法を創出できると確信する。