The role of Sirt-1 in development of calcific aortic valve stenosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08533
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Yamagata University
• Principal Investigator: Watanabe Tetsu 山形大学, 医学部, 准教授 (40359568)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 大動脈弁狭窄症 / 石灰化 / Sirt-1 / Shear stress / 長寿遺伝子 / 早期細胞老化 / 石灰化大動脈弁狭窄症

Outline of Final Research Achievements

The prevalence of aortic valve stenosis (AVS) is increasing with increasing the elderly population. However, effective drug therapy has not been established. Sirt-1 is reportedly involved in suppressing the development of age-related diseases. The relationship between Sirt-1 and the progression of calcific AVS has not been fully investigated. In this study, we investigate the role of Sirt-1 in the development of calcific AVS using porcine aortic valve interstitial cells. Furthermore, we examine Sirt-1 expression and aortic valve calcification using wire injury calcific AVS mouse model. We also examine whether administration of Sirt-1 activators can promote tissue repair, inhibit aortic valve leaflet remodeling, reduce aortic valve pressure gradient, and inhibit calcification.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

高齢人口の増加に伴い心不全患者が急増しており、その重要な原因の１つに大動脈弁狭窄症（AVS）の増加が挙げられる。AVSの危険因子は動脈硬化と共通するが、脂質低下療法を含めAVS進行抑制に有効な薬物療法がない。長寿遺伝子Sirt-1は加齢が関与する疾患の発症抑制に関与することが報告されているが、AVSの進行とSirt-1の関係は未だ不明である。本研究では、Sirt-1がAVSの進展抑制に果たす役割を明らかにする。Sirt-1活性化薬がAVS進展を抑制するか検討し、新しい治療法確立を目指す。