Hepatic inactivation of murine Surf4 results in marked reduction in plasma cholesterol.

ABSTRACT: PCSK9 negatively regulates low-density lipoprotein receptor (LDLR) abundance on the cell surface, leading to decreased hepatic clearance of LDL particles and increased levels of plasma cholesterol. We previously identified SURF4 as a cargo receptor that facilitates PCSK9 secretion in HEK293T cells (Emmer et al., 2018). Here, we generated hepatic SURF4-deficient mice (Surf4^fl/fl Alb-Cre⁺) to investigate the physiologic role of SURF4 in vivo. Surf4^fl/fl Alb-Cre⁺ mice exhibited normal viability, gross development, and fertility. Plasma PCSK9 levels were reduced by ~60% in Surf4^fl/fl Alb-Cre⁺ mice, with a corresponding ~50% increase in steady state LDLR protein abundance in the liver, co

SUBMITTER: Tang VT 

PROVIDER: S-EPMC9581532 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature