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

LIU Su-su; YU Tong; QIAO Yan-fang; GU Shu-xiao; CHAI Xin-lou

doi:10.1007/s11655-023-3545-z

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

Review | Updated：2024-06-28

- Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets
- Chinese Journal of Integrative Medicine Vol. 30, Issue 7, Pages: 664-672(2024)
- Affiliations：
  
  School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing (102401), China
- Author bio：
  
  Prof. CHAI Xin-lou, E-mail: mmxin3@126.com
- Funds：
- DOI：10.1007/s11655-023-3545-z
  CLC：
- Published：2024-07，
  
  Published Online：13 March 2023，
  
  Accepted：21 November 2022
Scan for full text
LIU Su-su, YU Tong, QIAO Yan-fang, et al. Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets. [J]. Chinese Journal of Integrative Medicine 30(7):664-672(2024)
DOI：

LIU Su-su, YU Tong, QIAO Yan-fang, et al. Research on Hepatocyte Regulation of PCSK9-LDLR and Its Related Drug Targets. [J]. Chinese Journal of Integrative Medicine 30(7):664-672(2024) DOI： 10.1007/s11655-023-3545-z.

摘要

Abstract

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.

关键词

Keywords

hyperlipidemiaproprotein convertase subtilisin/kexin type 9low-density lipoprotein receptorintracellular pathwayextracellular pathway

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