Residual risk control in familial hypercholesterolemia: Identification of lipids responsible for HDL malignant transformation

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K08125
• 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: National Cardiovascular Center Research Institute
• Principal Investigator: Ogura Masatsune 国立研究開発法人国立循環器病研究センター, 研究所, 室長 (30532486)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: HDL機能 / 家族性高コレステロール血症 / 動脈硬化予防

Outline of Final Research Achievements

In this research project, we searched for the lipids that are responsible for making HDL bad in patients with familial hypercholesterolemia (FH). We have previously reported that cholesterol efflux capacity is a more useful residual risk marker than HDL-C levels in patients with FH. However, we faced the challenge of not being able to standardize the method for measuring the efflux capacity. We decided to overcome the problem by identifying the true bad lipids, which are common to both impaired efflux capacity and coronary artery disease, among the HDL components. Therefore, we performed lipidomic analysis of patient HDL fractions and identified several lipid species that were negatively associated with efflux capacity and positively associated with atherosclerosis severity.

Free Research Field

脂質代謝学

Academic Significance and Societal Importance of the Research Achievements

本研究の達成は引き抜き能に代わる動脈硬化予測バイオマーカーの確立や創薬（得られた脂質分子の阻害薬）の基盤を築く。家族性高コレステロール血症（FH）患者のHDL代謝は非FHと大きな差異はないため、全ハイリスク患者におけるLDL-C低下治療後の残余リスク制圧につながる。