Fazio Sergio
Cornelius Vanderbilt Professor of Medicine Professor of Pathology, Immunology, and Microbiology Chief, Section of CVD Prevention Vanderbilt University School of Medicine, Nashville, Tennessee, USA.
Atheroscler Suppl. 2015 Feb;17:23-6. doi: 10.1016/S1567-5688(15)50006-8.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a major role in the regulation of lipoprotein metabolism, mostly through control of low-density lipoprotein receptor degradation. Depletion of cellular cholesterol causes a compensatory increase in plasma PCSK9 levels, which can diminish the cholesterol-lowering power of statins and may lead to the overproduction of intestinal lipoproteins, mainly thorough the up regulation of microsomal triglyceride transfer protein and the Niemann-Pick C1-like 1 protein, the target of ezetimibe. Thus, ezetimibe therapy may counter this unwanted effect of statins, providing an additional theoretical rationale for combining the effect of ezetimibe on intestinal cholesterol absorption and that of statins on cholesterol synthesis.
前蛋白转化酶枯草溶菌素/kexin 9型（PCSK9）在脂蛋白代谢调节中起主要作用，主要通过控制低密度脂蛋白受体的降解来实现。细胞内胆固醇的消耗会导致血浆PCSK9水平代偿性升高，这会削弱他汀类药物的降胆固醇能力，并可能导致肠道脂蛋白过度产生，主要是通过上调微粒体甘油三酯转运蛋白和依折麦布的作用靶点尼曼-匹克C1样1蛋白来实现。因此，依折麦布治疗可能会抵消他汀类药物的这种不良作用，为将依折麦布对肠道胆固醇吸收的作用与他汀类药物对胆固醇合成的作用相结合提供了额外的理论依据。
