McKenney James M
National Clinical Research, Inc., School of Pharmacy, Virginia Commonwealth University, Richmond, VA, USA.
J Clin Lipidol. 2015 Mar-Apr;9(2):170-86. doi: 10.1016/j.jacl.2015.01.001. Epub 2015 Jan 13.
Inhibitors of proprotein convertase subtilisin kexin type 9 (PCSK9) represent a new therapeutic category of drugs for the treatment of dyslipidemia and atherosclerotic cardiovascular disease. To appreciate the efficacy of these agents and interpret research results, it is important to understand the dynamic relationship between PCSK9, low-density lipoprotein-receptors, intrahepatic cholesterol synthesis, and blood cholesterol levels. Drugs which negate the action of PCSK9 can produce substantial reductions in atherogenic lipoprotein cholesterol-carrying particles and thereby hold the potential for further reducing events associated with atherosclerotic cardiovascular disease. This article will describe and discuss PCSK9 interactive mechanisms and apply them to the interpretation of clinical trial results, which involve PCSK9 monoclonal antibodies.
前蛋白转化酶枯草溶菌素9型（PCSK9）抑制剂代表了一类用于治疗血脂异常和动脉粥样硬化性心血管疾病的新型治疗药物。为了了解这些药物的疗效并解读研究结果，了解PCSK9、低密度脂蛋白受体、肝内胆固醇合成和血液胆固醇水平之间的动态关系非常重要。能够抵消PCSK9作用的药物可使致动脉粥样硬化的携带脂蛋白胆固醇的颗粒大幅减少，从而有可能进一步降低与动脉粥样硬化性心血管疾病相关的事件。本文将描述和讨论PCSK9的相互作用机制，并将其应用于对涉及PCSK9单克隆抗体的临床试验结果的解读。
