Elucidation of the mechanism by which NRDC, a multifunctional protease, regulates platelet production and its significance as a diagnostic marker for ACS in the hyperacute phase.

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08445
• 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: Shiga University of Medical Science
• Principal Investigator: Mikiko Ohno 滋賀医科大学, 医学部, 准教授 (10583198)
• Co-Investigator(Kenkyū-buntansha): 西 英一郎 滋賀医科大学, 医学部, 教授 (30362528)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 急性冠症候群 / 血小板 / 多機能プロテアーゼ

Outline of Final Research Achievements

Nardilysin (NRDC) is a multifunctional protease that is secreted during the very early phase of acute coronary syndromes (ACS). Platelets, essential components in thrombus formation, are generated through platelet shedding, involving the release of cytoplasm from mature megakaryocytes in the bone marrow. Recent findings indicate that NRDC secretion from mature megakaryocytes is stimulated by turbulence, positively influencing platelet shedding. Moreover, the enzymatic activity of NRDC is important for the platelet shedding. In this study, we aimed to investigate the mechanisms underlying platelet production mediated by NRDC, elucidate the significance of its enzymatic activity, and explore the role of platelets and secreted NRDC in ACS. Through comprehensive research employing genetically engineered mice, we conducted basic investigations, alongside prospective clinical studies assessing NRDC as a potential diagnostic biomarker for ACS.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

ACSの本態はプラーク破裂を契機とする血栓形成にあり、血小板が重要な役割を有する。ACS発症時の血小板数増加が多くの臨床論文で示されたがその機序は明らかではなかった。NRDCは血小板産生促進因子であることから、ACSにおける血小板増加が、NRDC分泌亢進（血清濃度上昇）を介して生じている可能性が示唆された。乱流刺激によって巨核球からNRDCが分泌される機構やACSで分泌が亢進する意義を明らかにすることで、NRDCのホルモン様作用について解明できる可能性がある。これらの機序を明らかにすることで、抗NRDC抗体や酵素活性を抑制する小分子化合物などの新規治療法の開発につながる可能性がある。