载脂蛋白代谢相关蛋白 9（PCSK9）在高脂血症和动脉粥样硬化中的结构与功能。
Structure and Function of Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in Hyperlipidemia and Atherosclerosis.
机构信息
The Mary and Garry Weston Molecular Immunology Laboratory, Thrombosis Research Institute, London, SW3 6LR, United Kingdom.
出版信息
Curr Drug Targets. 2019;20(10):1029-1040. doi: 10.2174/1389450120666190214141626.
BACKGROUND
One of the important factors in Low-Density Lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9) is a newly discovered serine protease that destroys LDLR in the liver and thereby controls the levels of LDL in plasma. Inhibition of PCSK9-mediated degradation of LDLR has, therefore, become a novel target for lipid-lowering therapy.
METHODS
We review the current understanding of the structure and function of PCSK9 as well as its implications for the treatment of hyperlipidemia and atherosclerosis.
RESULTS
New treatments such as monoclonal antibodies against PCSK9 may be useful agents to lower plasma levels of LDL and hence prevent atherosclerosis.
CONCLUSION
PCSK9's mechanism of action is not yet fully clarified. However, treatments that target PCSK9 have shown striking early efficacy and promise to improve the lives of countless patients with hyperlipidemia and atherosclerosis.
背景
低密度脂蛋白（LDL）代谢的一个重要因素是 LDL 受体（LDLR），它能够结合并随后清除循环中 LDL（LDL-C）衍生的胆固醇。前蛋白转化酶枯草溶菌素 9（PCSK9）是一种新发现的丝氨酸蛋白酶，它在肝脏中破坏 LDLR，从而控制血浆中的 LDL 水平。因此，抑制 PCSK9 介导的 LDLR 降解已成为降脂治疗的新靶点。
方法
我们综述了 PCSK9 的结构和功能的最新认识及其在治疗高脂血症和动脉粥样硬化中的意义。
结果
针对 PCSK9 的新型治疗方法，例如单克隆抗体，可能是降低血浆 LDL 水平、从而预防动脉粥样硬化的有用药物。
结论
PCSK9 的作用机制尚未完全阐明。然而，针对 PCSK9 的治疗方法已显示出早期显著的疗效，并有望改善无数患有高脂血症和动脉粥样硬化患者的生活。
Zotero 插件