Effects of DNA aptamer raised against advanced glycation end products on arterial restenosis

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17729
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Showa University
• Principal Investigator: Kushima Hideki 昭和大学, 医学部, 兼任講師 (70792696)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 糖尿病 / 再狭窄 / マウスモデル / アプタマー / 終末糖化産物 / RAGE

Outline of Final Research Achievements

Advanced glycation end products (AGEs) are formed through a non-enzymatic glycation reaction of proteins, the process of which can be accelerated by aging or diabetes. Many studies have revealed that AGEs are associated with increased risks for many diseases including atherosclerotic cardiovascular disease. Angioplasty is a procedure to open narrow coronary arteries caused by atherosclerosis. However, diabetes is shown to be a risk for restenosis after angioplasty, which can result in a failure of angioplasty. Recently, we developed DNA aptamers that can inhibit toxic effects of AGEs through directly binding to AGEs or receptor for AGEs (RAGE). In this study, we treated KK-Ay mice, a model of obesity-induced diabetes, with these aptamers. We found that, compared to control aptamer, AGEs neutralizing DNA aptamer and RAGE inhibitory DNA aptamer prevented restenosis after femoral artery wire injury.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

日本では、成人の6人に1人が糖尿病あるいはその予備軍であると推察されており、人口の高齢化によってこの割合はさらに増加していくと予想される。このため、糖尿病の合併症への対策は重要な問題である。DNAアプタマーは、抗体医薬品に比べて安価で、大量に調整もできることから、次世代のバイオ医薬品として注目を集めている。本研究から、糖尿病患者における血管形成術後の再狭窄に対しするAGEs中和DNAアプタマーとRAGE阻害DNAアプタマーの有用性が示され、新たな治療法の開発につながると予想される。