Premium
Activation of the farnesoid X receptor represses PCSK9 expression in human hepatocytes
Author(s) -
Langhi Cédric,
Le May Cédric,
Kourimate Sanae,
Caron Sandrine,
Staels Bart,
Krempf Michel,
Costet Philippe,
Cariou Bertrand
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.02.038
Subject(s) - farnesoid x receptor , pcsk9 , chenodeoxycholic acid , kexin , proprotein convertase , chemistry , bile acid , agonist , cyp8b1 , receptor , endocrinology , medicine , ldl receptor , g protein coupled bile acid receptor , biology , cholesterol , nuclear receptor , biochemistry , transcription factor , lipoprotein , gene
The purpose of this study was to determine whether bile acids (BAs) modulate hepatic pro‐protein convertase subtilisin/kexin 9 (PCSK9) gene expression. Immortalized human hepatocytes were treated with various BAs. Chenodeoxycholic acid (CDCA) treatment specifically decreased both PCSK9 mRNA and protein contents. Moreover, activation of the BA‐activated farnesoid X receptor (FXR) by its synthetic specific agonist GW4064 also decreased PCSK9 expression. Of functional relevance, coadministration of CDCA counteracted the statin‐induced PCSK9 expression, leading to a potentiation of LDL receptor activity. This study suggests that a transcriptional repression of PCSK9 by CDCA or FXR agonists may potentiate the hypolipidemic effect of statins.