The next generation of novel low-density lipoprotein cholesterol-lowering agents: proprotein convertase subtilisin/kexin 9 inhibitors.
The next generation of novel low-density lipoprotein cholesterol-lowering agents: proprotein convertase subtilisin/kexin 9 inhibitors.
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DOI：
10.1016/j.phrs.2013.04.001
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发表时间：
2013-07
影响因子：
9.3
通讯作者：
Li Shen;Hongchun Peng;Danyan Xu;Shuiping Zhao
中科院分区：
文献类型：
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作者：
Li Shen;Hongchun Peng;Danyan Xu;Shuiping Zhao
前蛋白转化酶枯草杆菌蛋白酶/kexin 9（PCSK 9）已被证明可以降解肝脏低密度脂蛋白受体（LDLR）。功能获得性突变促进家族性高胆固醇血症的发展，而功能丧失性突变与循环低密度脂蛋白胆固醇（LDL-C）水平降低和对冠心病的显著保护相关。主要类别的常用处方降脂药物（如他汀类药物）会增加血清PCSK 9水平，因此PCSK 9抑制会增加他汀类药物降低LDL-C的疗效。因此，PCSK 9是新一代降胆固醇药物的一个有吸引力的治疗靶点。在这里，我们简要概述了PCSK 9抑制剂的发展，并强调了目前处方的LDL-C降低药物对PCSK 9的影响，以及正在探索的治疗抑制策略。目前的研究和临床试验结果表明，PCSK 9抑制剂可能是一种令人兴奋的治疗血脂异常和相关心血管疾病的新治疗药物。
Proprotein convertase subtilisin/kexin 9 (PCSK9) has been shown to degrade hepatic low-density lipoprotein receptors (LDLR). Gain-of-function mutations promote the development of familial hypercholesterolemia, whereas loss-of-function mutations are associated with lower levels of circulating low-density lipoprotein cholesterol (LDL-C) and significant protection against coronary heart disease. The major classes of commonly prescribed lipid-lowering medications, such as statins, increase serum PCSK9 levels, thus PCSK9 inhibition would increase the efficacy of statins on LDL-C lowering. Therefore, PCSK9 is an attractive therapeutic target for the new generation of cholesterol-lowering drugs. Here, we present a brief overview of the development of PCSK9 inhibitors and highlight the effect of currently prescribed LDL-C-lowering drugs on PCSK9, and the strategies that are being explored for its therapeutic inhibition. Current research and clinical trial results indicate that a PCSK9 inhibitor may be an exciting new therapeutic drug for the treatment of dyslipidemia and relevant cardiovascular diseases.