Targeting Liver Epsins Ameliorates Dyslipidemia in Atherosclerosis through Inhibition of Proprotein Convertase Subtilisin/Kexin Type 9-Mediated Low-density Lipoprotein Receptor Degradation.

ABSTRACT:

Background

The low-density lipoprotein receptor (LDLR) in the liver plays a crucial role in clearing low-density lipoprotein cholesterol (LDL-C) from the bloodstream. This process takes place mainly in the liver. Under atherogenic conditions, Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9), secreted by the liver, binds to LDLR on hepatocytes, preventing its recycling and enhancing its lysosomal degradation. This process reduces LDL-C clearance, promoting hypercholesterolemia. Epsins, a family of ubiquitin-binding endocytic adaptors, are key regulators of atherogenesis in lesional cells, including endothelial cells and macrophages. Given epsins' canonical role in regulating endocytosis of cell surface receptors, we aimed to determine whether and how liver epsins contribute to

SUBMITTER: Zhu B 

PROVIDER: S-EPMC11383288 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature