Inazu Akihiro
Department of Clinical Laboratory Science, Graduate School of Medical Science, Kanazawa University.
J Atheroscler Thromb. 2025 Aug 1;32(8):911-923. doi: 10.5551/jat.RV22037. Epub 2025 May 29.
Cholesteryl ester transfer protein (CETP) deficiency and lipoprotein phenotypes with CETP inhibitors were compared. The effects on atherosclerotic cardiovascular disease (ASCVD) and the recently suggested retinal disease of age-related macular degeneration (ARMD) were summarized and discussed in relation to CETP deficiency and extremely increased high-density lipoprotein (HDL) cholesterol levels (＞100 mg/dL). In CETP truncated variants leading to reduced low-density lipoprotein cholesterol levels, ASCVD risk was decreased in heterozygotes. ASCVD prevalence did not increase in homozygotes with CETP deficiency. However, the association between ASCVD and ARMD risks in cases of very high HDL cholesterol level found in multifactorial hyperalphalipoproteinemia needs to be clarified on an etiological basis. The hurdles facing the development of CETP inhibitors are summarized, including a new result for obicetrapib.
对胆固醇酯转运蛋白（CETP）缺乏症和使用CETP抑制剂后的脂蛋白表型进行了比较。总结并讨论了CETP缺乏症和高密度脂蛋白（HDL）胆固醇水平极度升高（＞100mg/dL）对动脉粥样硬化性心血管疾病（ASCVD）以及最近提出的年龄相关性黄斑变性（ARMD）视网膜疾病的影响。在导致低密度脂蛋白胆固醇水平降低的CETP截短变体中，杂合子的ASCVD风险降低。CETP缺乏症的纯合子中ASCVD患病率并未增加。然而，在多因素高α脂蛋白血症中发现的HDL胆固醇水平极高的情况下，ASCVD与ARMD风险之间的关联需要从病因学角度加以阐明。总结了CETP抑制剂开发面临的障碍，包括奥贝胆酸的一项新结果。
