Clinical utility of cholesterol uptake capacity, a novel indicator for HDL functionality

• Project/Area Number: 18K08073
• 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: Kobe University
• Principal Investigator: Toh Ryuji 神戸大学, 医学研究科, 特命准教授 (50379418)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 高比重リポ蛋白(HDL) / コレステロール取り込み能 / 動脈硬化 / 高比重リポ蛋白（HDL) / 心血管病 / 高比重リポ蛋白 / コレステロール逆転送

Outline of Final Research Achievements

Cholesterol efflux from atherosclerotic lesion is a key function of high-density lipoprotein (HDL). Recently, we established a simple, high-throughput, cell-free assay to evaluate the capacity of HDL to accept additional cholesterol, which is herein referred to as “cholesterol uptake capacity (CUC)”. We investigated the cross-sectional relationship between CUC and the morphological features of angiographic stenosis by OCT, and revealed that CUC was inversely related to lipid-rich plaque burden and the extent of macrophage accumulation. We also demonstrated that impaired CUC is the risk for incidence of target-lesion revascularization.

Academic Significance and Societal Importance of the Research Achievements

HDLはコレステロール引抜きに加え多彩な抗動脈硬化作用を有するも、慢性炎症や糖尿病などの病態下では「善玉」としての作用が失われ、「機能不全HDL」となる。HDLの重要性は、量のみならず、質も併せて評価すべきであると変遷しているにもかかわらず、いまだ確立されたHDL機能評価法がないこと自体がHDL研究の大きな障壁となっている。本研究成果は「機能不全HDL」を簡便かつ再現性をもって検出することを可能とし、動脈硬化性疾患のリスク指標としてのHDLの意義についてリアルワールド・エビデンスの構築に寄与することのみならず、HDL機能改善を標的とした創薬に強力な研究基盤技術を提供することが期待される。

Research Products

• [Journal Article] Fibronectin-containing High-Density Lipoprotein is Associated with Cancer Cell Adhesion and Proliferation (2020)
  • Author(s): Eriko Hisamatsu, Manabu Nagao, Ryuji Toh, Yasuhiro Irino, Takuya Iino, Tetsuya Hara, Hidekazu Tanaka, Seimi Satomi-Kobayashi, Tatsuro Ishida, Ken-Ichi Hirata
  • Journal Title: Kobe J Med Sci . Volume: 66
  • Peer Reviewed
• [Journal Article] Association of cholesterol uptake capacity, a novel indicator for HDL functionality, and coronary plaque properties: An optical coherence tomography-based observational study (2020)
  • Author(s): Oshita T、Toh R、Nagano Y、Kuroda K、Nagasawa Y、Harada A、Murakami K、Kiriyama M、Yoshikawa K、Miwa K、Kubo T、Iino T、Nagao M、Irino Y、Hara T、Shinohara M、Otake H、Shinke T、Nakajima K、Ishida T、Hirata Ken-ichi
  • Journal Title: Clinica Chimica Acta Volume: 503 Pages: 136-144
  • DOI: 10.1016/j.cca.2020.01.001
  • NAID: 120006824021
  • Peer Reviewed
• [Journal Article] Serum concentration of full-length- and carboxy-terminal fragments of endothelial lipase predicts future cardiovascular risks in patients with coronary artery disease (2019)
  • Author(s): Nagao Manabu、Miyashita Kazuya、Mori Kenta、Irino Yasuhiro、Toh Ryuji、Hara Tetsuya、Hirata Ken-ichi、Shinohara Masakazu、Nakajima Katsuyuki、Ishida Tatsuro
  • Journal Title: Journal of Clinical Lipidology Volume: 13 Issue: 5 Pages: 839-846
  • DOI: 10.1016/j.jacl.2019.07.007
  • NAID: 120007002630
  • Peer Reviewed
• [Journal Article] Impaired Cholesterol‐Uptake Capacity of HDL Might Promote Target‐Lesion Revascularization by Inducing Neoatherosclerosis After Stent Implantation (2019)
  • Author(s): Nagano Y, Otake H, Toba T, Kuroda K, Shinkura Y, Tahara N, Tsukiyama Y, Yanaka K, Yamamoto H, Nagasawa A, Onishi H, Sugizaki Y, Takeshige R, Harada A, Murakami K, Kiriyama M, Oshita T, Irino Y, Kawamori H, Ishida T, Toh R, Shinke T, Hirata KI.
  • Journal Title: Journal of the American Heart Association Volume: 8 Issue: 9
  • DOI: 10.1161/jaha.119.011975
  • NAID: 120006733129
  • Peer Reviewed / Open Access
• [Presentation] Comparison of Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality, and Cholesterol Efflux Capacity in Association with Coronary Plaque Properties (2019)
  • Author(s): Toshihiko Oshita, Ryuji Toh, Mitsumasa Okano, Koichi Watanabe, Yuichiro Nagano, Amane Harada, Katsuhiro Murakami, Seimi Kobayashi, Masakazu Shinohara, Tetsuya Hara, Yasuhiro Irino, Hiromasa Otake,Tatsuro Ishida, Ken-ichi Hirata.
  • Organizer: 第83回 日本循環器学会学術集会
• [Presentation] HDL機能の新規評価法“Cholesteroluptakecapacity”とOCT解析によ る冠動脈プラーク病変性状の比較検討 (2018)
  • Author(s): 尾下寿彦、杜隆嗣、入野康宏、黒田浩史、永野雄一郎、長澤圭典、大竹寛雅、新家俊郎、石田達郎、平田健一
  • Organizer: 第55回 日本臨床分子医学会学術集会
• [Presentation] Understanding of HDL Cholesterol Efflux Capacity: Towards Clinical Application (2018)
  • Author(s): Ryuji Toh, Tatsuro Ishida, Ken-ichi Hirata
  • Organizer: 第50回 日本動脈硬化学会総会・学術集会
  • Invited
• [Presentation] Searching for modulating factor of cholesterol uptake capacity, a novel indicator for HDL functionality (2018)
  • Author(s): Toshihiko Oshita, Ryuji Toh,Mitsumasa Okano, Shigeyasu Tsuda, Koichi Watanabe, Seimi Kobayashi, Tetsuya Hara, Masakazu Shinohara, Yasuhiro Irino, Katsuhiro Murakami, Amane Harada, Tatsuro Ishida, Ken-ichi Hirata
  • Organizer: 第50回 日本動脈硬化学会総会・学術集会
• [Presentation] Cholesterol Uptake Capacity, a Novel Indicator for HDL Functionality, Versus Cholesterol Efflux Capacity in Association with Coronary Plaque Lipid (2018)
  • Author(s): Toshihiko Oshita, Ryuji Toh, Mitsumasa Okano, Koichi Watanabe, Yuichiro Nagano, Amane Harada, Katsuhiro Murakami, Seimi Kobayashi, Masakazu Shinohara, Tetsuya Hara, Yasuhiro Irino, Hiromasa Otake,Tatsuro Ishida, Ken-ichi Hirata.
  • Organizer: American Heart Association Scientific Sessions 2018
  • Int'l Joint Research