Analysis of molecular mechanism of cholesterol metabolism associated with red blood cell.(Fostering Joint International Research)

• Project/Area Number: 16KK0198
• Research Category: Fund for the Promotion of Joint International Research (Fostering Joint International Research)
• Allocation Type: Multi-year Fund
• Research Field: Laboratory medicine
• Research Institution: Tokyo Medical and Dental University
• Principal Investigator: Ryunosuke Ohkawa 東京医科歯科大学, 大学院医歯学総合研究科, 教授 (50420203)
• Project Period (FY): 2017 – 2020
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥14,950,000 (Direct Cost: ¥11,500,000、Indirect Cost: ¥3,450,000)
• Keywords: 赤血球 / 脂質代謝 / コレステロール / トランスポーター / コレステロール代謝 / ABCトランスポーターA1 / アポリポタンパクA-I結合タンパク / 粥状動脈硬化

Outline of Final Research Achievements

Previous study suggested that red blood cells are deeply associated with lipid metabolism. However, the mechanism had not been fully understood. In this study, we started an international collaboration research in Baker Heart and Diabetes Institute in Australia from Sep. 21st,2017 to Sep. 26th, 2018. As a result, we found that red blood cells release cholesterol dramatically and actively to plasma, play a role in reverse cholesterol transport system and some transporters on their membrane could be involved in this lipid metabolism. I also built the research network with Alan T. Remaley in NIH.

Academic Significance and Societal Importance of the Research Achievements

本研究により，予想通り赤血球はこれまで報告されていた以上に生体内でのコレステロールを中心とした脂質代謝に関わっていることが明らかになった．現在，脂質異常症の検査として，血清中のリポタンパクコレステロール濃度の測定が主に行われており，赤血球を対象とした脂質検査は行われていない．本研究によって築き上げられた国際ネットワークを活かし，今回明らかになった赤血球によるコレステロール放出能やトランスポーターについてさらに追及することで，新たな脂質異常症検査の開発に繋がると考えられる．

Research Products

• [Int'l Joint Research] ベイカーIDI心臓・糖尿病研究所(オーストラリア) (2017)
  • Year and Date: 2017-09-21
• [Journal Article] Cholesterol Efflux-Independent Modification of Lipid Rafts by AIBP (Apolipoprotein A-I Binding Protein) (2020)
  • Author(s): Low Hann、Mukhamedova Nigora、Capettini Luciano dos Santos Aggum、Xia Yining、Carmichael Irena、Cody Stephen H.、Huynh Kevin、Ditiatkovski Michael、Ohkawa Ryunosuke、Bukrinsky Michael、Meikle Peter J.、Choi Soo-Ho、Field Seth、Miller Yury I.、Sviridov Dmitri
  • Journal Title: Arteriosclerosis, Thrombosis, and Vascular Biology Volume: 40 Issue: 10 Pages: 2346-2359
  • DOI: 10.1161/atvbaha.120.315037
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Cholesterol transport between red blood cells and lipoproteins contributes to cholesterol metabolism in blood (2020)
  • Author(s): Ohkawa, R., Low, H., Mukhamedova, N., Fu, Y., Lai, S.J., Sasaoka, M., Hara, A., Yamazaki, A., Kameda, T., Horiuchi, Y., Meikle, J.P., Pernes, G., Lancaster, G.I., Ditiatkovski, M., Nestel, P., Vaisman, B.L., Sviridov, D., Murphy, A.J., Remaley, A.T., Sviridov, D., and Tozuka, M
  • Journal Title: Journal of Lipid Research Volume: 61 Issue: 12 Pages: 1577-1588
  • DOI: 10.1194/jlr.ra120000635
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Evaluation of cholesterol uptake and efflux by red blood cells. (2020)
  • Author(s): Ohkawa R., Low H., Mukhamedova N., Fu Y., Lai SJ., Sasaoka M., Horiuchi Y., Ditiatkovski M., Nestel P., Sviridov D., and Tozuka M
  • Organizer: 2020 AACC Annual Scientific Meeting & Clinical Lab Expo
  • Int'l Joint Research
• [Presentation] 赤血球膜コレステロール含有量測定法の検討 (2020)
  • Author(s): 山崎 あずさ，堀内 優奈，賴 劭睿，亀田 貴寛，市村 直也，東田 修二，大川 龍之介
  • Organizer: 第67回日本臨床検査医学会学術集会
• [Presentation] Various types of research networks for medical technology (2020)
  • Author(s): Ohkawa R.
  • Organizer: the 5th congress of AASMT
  • Int'l Joint Research / Invited
• [Remarks] 先端分析検査学分野ホームページ
  • URL: https://www.tmd.ac.jp/gradh/alc/index.html
• [Remarks] Lipoproteins and Atherosclerosis研究室のホームページ
  • URL: https://baker.edu.au/research/laboratories/lipoproteins-atherosclerosis