Exploring microRNA targeting calcified coronary artery lesions in chronic kidney disease

• Project/Area Number: 17K09563
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Kanazawa Medical University
• Principal Investigator: AKAO Hironobu 金沢医科大学, 医学部, 准教授 (50398997)
• Project Period (FY): 2017-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 石灰化冠動脈病変 / 慢性腎臓病 / microRNA / エクソソーム / 次世代シーケンサ― / microRNAs / 次世代シーケンサー

Outline of Final Research Achievements

Cardiovascular disease is the leading cause of death in chronic kidney disease (CKD) patients, and 50-60% of those suffer from coronary artery lesion, which is often difficult to treat because of its association with severe calcification. The purpose of this study is to elucidate the mechanisms underlying the development of arterial calcification with the aim of formulating new treatment strategies, which determine the prognosis of CKD patients. Specifically, we used blood samples containing molecules derived from atherosclerotic vessel walls that flow out to the body circulation after coronary artery rotablator therapy. This approach could identify microRNAs in exosomes involved in atherosclerosis in vivo by RNA-seq using a next-generation sequencer.

Academic Significance and Societal Importance of the Research Achievements

本研究の特色は動脈壁を切削前後に経時的に採取した血液検体サンプルを用いることである。動脈硬化巣における分子機構については、剖検例ならびに実験系における病理学的解析のみであり、臨床例を用いた解析は見当たらない。Rotablator施行後に、血管壁に存在する分子が体循環に流出し変動している事や、血液中の経時的なエクソソームmiRNAの挙動に着目して、証明した報告は国内外において前例がなく、血管壁内の動脈硬化巣にかかわるmiRNAを生体内で評価する革新的な研究である。さらに、進行した動脈硬化巣に存在するmiRNAの状態をヒト生体を対象に臨床的に評価することで治療法開発への貢献が期待される。

Research Products

• [Presentation] Local Interaction among Osteocalcin (OCN), Osteopontin (OPN) and Pentraxin 3 (PTX3) in Advanced Coronary Atherosclerosis: Coronary Rotational Atherectomy Study (2017)
  • Author(s): Hironobu Akao, Yasuhiko Saeki, Jun Sawaguchi, Minako Oda, Takaaki Takamura, Makoto Watanabe, Ryuhei Saito, Minoru Wakasa, Mizuho Iwadare, Ryouko Ishida, Nakaba Fujioka, Taketsugu Tsuchiya, Yasuyuki Kawai, Michihiko Kitayama, Kouji Kajinami
  • Organizer: 第49回日本動脈硬化学会総会・学術集会