Dynamism of HDL and its effect on atherosclerosis

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K07932
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52010:General internal medicine-related
• 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): 2019-04-01 – 2022-03-31
• Keywords: 高比重リポタンパク / 粥状動脈硬化 / バイオマーカー / 脂質代謝

Outline of Final Research Achievements

High-density lipoprotein (HDL) is a lipoprotein having various types of anti-atherosclerotic functions so that the cholesterol levels in HDL is measured for risk assessment of atherosclerosis. However, HDL is not homogeneous but heterogeneous particle. Each HDL contains different type/amount of proteins and lipids resulting in showing different characters and functions. Therefore, in addition to the quantification of cholesterol in whole HDL, we should understand each HDL in detail.
Current study revealed that consecutive reactions to HDL by two enzymes (myeloperoxidase and chymase) produced mainly two types of truncated apoA-I, which is main apolipoprotein of HDL. We also suggested that very low-density lipoprotein preferably transferred apoCs (regulators of triglyceride-degrading enzyme) to HDL, serum amyloid A modified HDL characters and functions dramatically, and the release of cholesterol from red blood cells affected each lipoprotein.

Free Research Field

臨床検査医学

Academic Significance and Societal Importance of the Research Achievements

現在，脂質異常症や粥状動脈硬化の進展の把握に高比重リポタンパクコレステロール濃度の定量が行われているが，一部の患者の病態しか反映されておらず，新たな心血管イベントの予測因子の発見が期待されている．
本研究で特定された特殊な条件下による断片化apoA-Iに対する抗体が作製されれば，粥状動脈硬化症の進行度を反映する新たな検査法の開発に繋がる可能性がある．また，血中で常に接触している他のリポタンパクや赤血球との相互作用，炎症性タンパクによるHDLの性質・機能への影響を明らかにしたことは，脂質異常症や粥状動脈硬化進展のメカニズムのさらなる解明に繋がるものと考えられる．