The effect of telomerase in the development of aortic valve stenosis

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K09503
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Ehime University
• Principal Investigator: Aono Jun 愛媛大学, 医学部附属病院, 講師(病院教員) (70512169)
• Co-Investigator(Kenkyū-buntansha): 末廣 千佳 愛媛大学, 医学部附属病院, 医員 (00770356) ; 坂上 智城 愛媛大学, 医学系研究科, 寄附講座講師 (40725917)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 大動脈弁狭窄症 / テロメラーぜ / TERT / 大動脈弁間質細胞

Outline of Final Research Achievements

To determine the role of telomerase, especially the catalytic subunit telomerase reverse transcriptase or abbreviated TERT, human aortic valve and valvular interstitial cells (VICs) isolated from aortic valve stenosis (AS) were investigated. The data base for unveiling the mechanism in the development of AS was created from histological, biochemical findings, and patient characteristics. Immunohistochemical analysis was performed using anti-TERT antibody. The expression of TERT was detected in the endothelial cells and interstitial cell in the calcified and sclerotic lesion. Microarray data from VICs showed the increase gene expression of 54kD Lipid metabolism enzyme Y in the VICs derived from calcified lesion of AS valve. The enzyme Y also has been reported to regulate the expression of TERT. Analyzing the microarray data, the investigation for the function of TERT is going to proceed, focusing on aortic valve endothelial and interstitial cells.

Free Research Field

動脈硬化関連疾患・心不全

Academic Significance and Societal Importance of the Research Achievements

テロメラーゼはテロメア長の調節に必須であり、細胞老化にも大きく関わっている。また癌を含めた炎症/増殖性疾患の発症・進展に関与することが報告されている。大動脈弁狭窄症(Aortic valve stenosis: AS)は加齢により心臓弁膜の硬化/狭窄を生じ突然死・急性心不全など致命的病態を生じる最重症心疾患の一つである。ASにおけるテロメラーゼの役割が明らかになれば、これらをターゲットとした手術適応『前段階』のAS患者のための創薬・バイオマーカーイノベーションを含めた発症・進行予防治療戦略を確立する上で大きな意義を持つものと期待される。