Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets

作     者：LIU Su-su YU Tong QIAO Yan-fang GU Shu-xiao CHAI Xin-lou 

作者机构：School of Traditional Chinese MedicineBeijing University of Traditional Chinese MedicineBeijing102401China 

出 版 物：《Chinese Journal of Integrative Medicine》 (中国结合医学杂志（英文版）)

年 卷 期：2024年第30卷第7期

页      面：664-672页

核心收录：

学科分类：100506[医学-中医内科学] 1006[医学-中西医结合] 1005[医学-中医学] 1002[医学-临床医学] 10[医学] 100602[医学-中西医结合临床] 

基　　金：Supported by National Science and Technology Major Special Project Based on Big Data Research and Development of New Chinese Medicine Drugs(No.2019ZX09201004-001-021) 

主　　题：hyperlipidemia proprotein convertase subtilisin/kexin type 9 low-density lipoprotein receptor intracellular pathway extracellular pathway 

摘      要：The prevalence of hyperlipidemia has increased significantly due to genetic, dietary, nutritional and pharmacological factors, and has become one of the most common pathological conditions in humans. Hyperlipidemia can lead to a range of diseases such as atherosclerosis, stroke, coronary heart disease, myocardial infarction, diabetes, and kidney failure, etc. High circulating low-density lipoprotein cholesterol (LDL-C) is one of the causes of hyperlipidemia. LDL-C in the blood binds to LDL receptor (LDLR) and regulates cholesterol homeostasis through endocytosis. In contrast, proprotein convertase subtilisin/kexin type 9 (PCSK9) mediates LDLR degradation via the intracellular and extracellular pathways, leading to hyperlipidemia. Targeting PCSK9-synthesizing transcription factors and downstream molecules are important for development of new lipid-lowering drugs. Clinical trials regarding PCSK9 inhibitors have demonstrated a reduction in atherosclerotic cardiovascular disease events. The purpose of this review was to explore the target and mechanism of intracellular and extracellular pathways in degradation of LDLR and related drugs by PCSK9 in order to open up a new pathway for the development of new lipid-lowering drugs.