Establishment of a histopathological diagnostic method for detecting high-risk patients with acute coronary syndrome

• Project/Area Number: 18K08123
• 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: University of Miyazaki
• Principal Investigator: Nishihira Kensaku 宮崎大学, 医学部, 研究員 (60736312)
• Co-Investigator(Kenkyū-buntansha): 植田 初江 国立研究開発法人国立循環器病研究センター, 病院, 客員研究員 (40522983)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2020: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 急性冠症候群 / 循環器病学 / 動脈硬化 / 循環器病

Outline of Final Research Achievements

We investigated the histopathological finding of materials obtained during percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS) and evaluated the relationship between the histopathological finding and clinical features. Older thrombus found in aspirated coronary material was associated with impaired myocardial reperfusion and was an independent predictor of poor outcomes in patients with ACS. In the histopathological analysis, fibrin and von Willebrand factor on ruptured sites were major adhesive molecules.
Moreover, in the process of this study, we discovered the presence of oxidized low-density lipoprotein at lipid-rich plaque in an ACS patients with heterozygous familial hypercholesterolemia.

Academic Significance and Societal Importance of the Research Achievements

急性冠症候群症例の血管内カテーテル治療時に得られる吸引血栓やアテレクトミーの標本を組織学的に評価することで、予後の悪い高リスク群の患者を抽出できる可能性がある。さらにはこれらの標本の組織学的検討から、急性冠症候群患者において、動脈硬化巣が破綻し血栓形成・血管閉塞していく過程には、フィブリンとフォンビルブラント因子が重要な役割を担っていることが明らかとなり、これらを抑制することで病状悪化を抑制できる可能性がある。

Research Products

• [Journal Article] The feasibility and limitation of coronary computed tomographic angiography imaging to identify coronary lipid-rich atheroma in vivo: Findings from near-infrared spectroscopy analysis (2021)
  • Author(s): Kitahara Satoshi、Kataoka Yu、Miura Hiroyuki、Nishii Tatsuya、Nishimura Kunihiro、Noguchi Teruo、Yasuda Satoshi
  • Journal Title: Atherosclerosis Volume: 322 Pages: 1-7
  • DOI: 10.1016/j.atherosclerosis.2021.02.019
  • Peer Reviewed
• [Journal Article] Impact of 1 month of intensive lipid-lowering therapy on plaque composition evaluated using near-infrared spectroscopy (2021)
  • Author(s): Nishihira K, Kuriyama N, Shibata Y.
  • Journal Title: Eur Heart J Case Rep Volume: 5
  • DOI: 10.1093/ehjcr/ytaa569
  • Peer Reviewed / Open Access
• [Journal Article] Pathological features of ruptured coronary plaque and thrombus interfaces: fibrin and von Willebrand factor as platelet scaffolds on rupture sites (2021)
  • Author(s): Yamashita A, Nishihira K, Gi T, Maekawa K, Hatakeyama K, Horiuchi S, Wada K, Shibata Y, Asada Y.
  • Journal Title: Thrombosis and Haemostasis Volume: 121 Pages: 234-241
  • DOI: 10.1055/s-0040-1716539
  • Peer Reviewed / Open Access
• [Journal Article] In-stent restenosis following third-generation sirolimus-eluting stent implantation: first report analysed from imaging modalities and histopathological findings (2020)
  • Author(s): Yoshioka G, Nishihira K, Asada Y, Node K.
  • Journal Title: Eur Heart J Volume: 41 Pages: 1707-1707
  • DOI: 10.1093/eurheartj/ehaa142
  • Peer Reviewed
• [Journal Article] Visualization of a Rapidly Progressing Lipid-Rich Plaque Causing No-Reflow Phenomenon During Percutaneous Coronary Intervention ― Insights From Near-Infrared Spectroscopy and Histopathology ― (2020)
  • Author(s): Honda Yasuhiro, Nishihira Kensaku, Kuriyama Nehiro, Yamashita Atsushi, Asada Yujiro, Shibata Yoshisato.
  • Journal Title: Circ Rep Volume: 2 Issue: 1 Pages: 71-72
  • DOI: 10.1253/circrep.cr-19-0107 10.1253/circrep.CR-19-0107
  • NAID: 130007784337
  • ISSN: 2434-0790
  • Peer Reviewed / Open Access
• [Journal Article] Visualization of oxidized low-density lipoprotein at lipid-rich plaque in a ST-segment elevation myocardial infarction case with heterozygous familial hypercholesterolaemia: insights from near-infrared spectroscopy and histopathological analysis. (2019)
  • Author(s): Nishihira Kensaku, Yamashita Atsushi, Kataoka Yu, Shibata Yoshisato, Asada Yujiro
  • Journal Title: European Heart Journal Cardiovascular Imaging Volume: 20 Pages: 1316-1316
  • DOI: 10.1093/ehjci/jez156
  • Peer Reviewed
• [Journal Article] Indoleamine 2,3-dioxygenase 1 in coronary atherosclerotic plaque enhances tissue factor expression in activated macrophages (2018)
  • Author(s): Watanabe Yuki、Koyama Shohei、Yamashita Atsushi、Matsuura Yunosuke、Nishihira Kensaku、Kitamura Kazuo、Asada Yujiro
  • Journal Title: Res Pract Thromb Haemost Volume: 2 Pages: 726-735
  • DOI: 10.1002/rth2.12128
  • Peer Reviewed / Open Access
• [Presentation] The limitation of computed tomographic coronary angiography imaging to identify coronary lipid-rich atheroma in vivo: insights from computed tomographic coronary angiography and near-infrared spectroscopy analysis (2019)
  • Author(s): Kitahara S, Kataoka Y, Miura H, Honda S, Fujino M, Hosoda H, Nakao K, Yoneda S, Otsuka F, Kanaya T, Nishihira K, Asaumi Y, Noguchi T, Yasuda S
  • Organizer: AHA2019
  • Int'l Joint Research
• [Presentation] Relationship between thrombus age in aspirated coronary material and mid-term major adverse cardiovascular events in patients with acute myocardial infarction (2018)
  • Author(s): Kensaku Nishihira, Yoshisato Shibata, Atsushi Yamashita, Nehiro Kuriyama, Yujiro Asada
  • Organizer: XVIII International Symposium on Atherosclerosis
  • Int'l Joint Research