Clearing of atherogenic lipoprotein particles by the liver requires hepatic LDLR and LRP1. This review highlights recent studies that have expanded out understanding of the molecular regulation and metabolic functions of LDLR and LRP1 in the liver. Various proteins orchestrate the intracellular trafficking of LDLR and LRP1.

It is a cell-surface receptor that recognizes apolipoprotein B100 (ApoB100), which is embedded in the outer phospholipid layer of very low-density lipoprotein (VLDL), their remnants—i.e. intermediate-density lipoprotein (IDL), and LDL particles. The receptor also recognizes apolipoprotein E (ApoE) which is found in chylomicron remnants and ...

6 天之前 · Hepatic LDLR abundance is a central determinant of lipoprotein clearance. Dysregulation of the LDLR pathway is associated with hypercholesterolemia and development of atherosclerosis. Emerging post-transcriptional mechanisms that govern LDLR abundance offer potential new lipid-lowering strategies.

Pcsk9 is regulated by the transcription factor HNF1α, and our further detailed analyses suggest that increased mTORC1 activity leads to activation of PKCδ, reduced activity of HNF4α and HNF1α, decreased PCSK9 expression, and ultimately increased hepatic LDLR protein levels, which result in decreased circulating LDL levels.

2007年9月1日 · The question of whether mature sterol regulatory element binding protein-2 (SREBP-2) mediates transcriptional activation of the hepatic low density lipoprotein (LDL) receptor by thyroid hormone was investigated.

The amount of the low-density lipoprotein receptor (LDLR) on the surface of hepatocytes is the primary determinant of plasma low-density lipoprotein (LDL)-cholesterol level. Although the synthesis and cellular trafficking of the LDLR have been ...

2012年4月2日 · Since LDL catabolism is primarily mediated through the hepatic LDL receptor (LDLR) (5), this suggests that in early diabetes and metabolic syndrome hyperinsulinemia is associated with upregulation of hepatic LDLR, compensating for increased VLDL secretion and leading to no overall change in LDL levels.

2021年2月3日 · Low-density lipoprotein receptor-related protein-1 (LRP1) is a type 1 transmembrane protein that serves endocytic and signaling functions through mechanisms that are cell type and context-dependent. For example, in macrophages, LRP1 is an endocytosis receptor for the uptake of aggregated LDL and efferocytosis of dead cells ( 1 , 2 ).

Purpose of review: Clearing of atherogenic lipoprotein particles by the liver requires hepatic low-density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1). This review highlights recent studies that have expanded our understanding of the molecular regulation and metabolic functions of LDLR and LRP1 in the liver.

2020年6月4日 · Hepatic LDLr plays a critical role in the flow of macrophage-derived UC to feces, while the plasma increase of APOB-containing lipoproteins is unable to stimulate m-RCT.