ABSTRACT

Introduction

Cardiovascular disorders are one of the leading causes of mortality and morbidity worldwide. Recent advances showed a promising role of proprotein convertase subtilisin/kexin type 9 (PCSK9) as a critical player in regulating plasma LDL levels and lipid metabolism.

Areas covered

This review addresses the molecular functions of PCSK9 with a vision on the clinical progress of utilizing monoclonal antibodies and other biological approaches to block PCSK9 activity. The successful clinical trials with monoclonal antibodies are reviewed. Recent advances in (pre)clinical trials of other biological approaches, such as small interfering RNAs, are also discussed.

Expert opinion

Discovery of PCSK9 and clinical use of its inhibitors to manage lipid metabolism is a step forward in hypolipidaemic therapy. A better understanding of the molecular activity of PCSK9 can help to identify new approaches in the inhibition of PCSK9 expression/activity. Whether if PCSK9 plays a role in other cardiometabolic conditions may provide grounds for further development of therapies.

中文翻译：

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从分子机制到临床疗效，针对PCSK9降低胆固醇的生物学方法的进展和前景。

摘要

介绍

心血管疾病是全球死亡率和发病率的主要原因之一。最近的进展表明，前蛋白转化酶枯草杆菌蛋白酶/ kexin 9型（PCSK9）在调节血浆LDL水平和脂质代谢方面起着至关重要的作用。

覆盖区域

这篇综述通过利用单克隆抗体和其他生物学方法来阻断PCSK9活性的临床进展来解决PCSK9的分子功能。评论了单克隆抗体的成功临床试验。还讨论了其他生物学方法（如小干扰RNA）在（临床）临床试验中的最新进展。

专家意见

PCSK9的发现及其抑制剂在脂质代谢中的临床应用是降血脂治疗的一大进步。更好地了解PCSK9的分子活性可以帮助确定抑制PCSK9表达/活性的新方法。PCSK9是否在其他心脏代谢疾病中发挥作用，可能为进一步开发治疗方法提供依据。