PCSK9 deficiency reduces atherosclerosis, apolipoprotein B secretion, and endothelial dysfunction.

ABSTRACT: Proprotein convertase subtilisin/kexin type 9 (PCSK9) interacts directly with cytoplasmic apoB and prevents its degradation via the autophagosome/lysosome pathway. This process affects VLDL and LDL production and influences atherogenesis. Here, we investigated the molecular machinery by which PCSK9 modulates autophagy and affects atherogenesis. We backcrossed Pcsk9^-/- mice with atherosclerosis-prone Ldlr^-/-Apobec1^-/- (LDb) mice to generate Ldlr^-/-Apobec1^-/-Pcsk9^-/- (LTp) mice. Deletion of PCSK9 resulted in decreased hepatic apoB secretion, increased autophagic flux, and decreased plasma levels of IDL and LDL particles. The LDLs from LTp mice (LTp-LDLs) were less atherogenic and conta

SUBMITTER: Sun H 

PROVIDER: S-EPMC5794417 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature