The role of DNA damage in the development of aortic stenosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08494
• 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: Fukushima Medical University
• Principal Investigator: Ishida Takafumi 福島県立医科大学, 医学部, 教授 (40346482)
• Co-Investigator(Kenkyū-buntansha): 石田 万里 広島大学, 医系科学研究科(医), 准教授 (30359898)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: DNA損傷

Outline of Final Research Achievements

Although it is known that calcific aortic stenosis (AS) shares risk factors with atherosclerotic cardiovascular disease, many patients without those risk factors develop AS. Recent studies have shown that persistent activation of DNA damage response is required for senescence-associated secretory phenotype. This study aimed to examine the role of DNA damage in the development of AS. Peripheral mononuclear cells (MNCs) were isolated from patients with AS. Expression of gamma-H2AX was measured by immunofluorescence, and dicentric chromosomes (DICs) were assayed using a fluorescent in situ hybridization technique. The numbers of gamma-H2AX foci and DICs were higher in the MNCs from AS patients than those from control subjects. The mRNA expressions of inflammatory cytokines were increased in MNCs from AS compared to those from control subjects. DNA damage may be involved in the mechanism underlying the progression of AS.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

今日のASのほとんどは石灰化ASであり、その基本病態である石灰化による弁の硬化の危険因子は冠動脈疾患、すなわち動脈硬化の危険因子とほとんど重複しているが、実際の石灰化AS患者においてはASと動脈硬化の程度がかい離していることも多く、未だ同定されていない因子がASの発症や進行に大 きく関与している可能性が高い。本研究の結果から、ASの発症にDNA損傷が関与している可能性があり、新たな治療標的になり得る可能性が示唆された。