Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Chenodeoxycholic Acid / pharmacology*
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DNA-Binding Proteins / agonists*
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Hepatocytes / drug effects*
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Hepatocytes / enzymology
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
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Isoxazoles / pharmacology
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Pravastatin / pharmacology
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Proprotein Convertase 9
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Proprotein Convertases
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RNA, Messenger / antagonists & inhibitors
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RNA, Messenger / metabolism
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Receptors, Cytoplasmic and Nuclear / agonists*
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Receptors, LDL / agonists
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Receptors, LDL / metabolism
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Serine Endopeptidases / genetics*
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Serine Endopeptidases / metabolism
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Transcription Factors / agonists*
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Transcription, Genetic / drug effects*
Substances
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DNA-Binding Proteins
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Isoxazoles
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RNA, Messenger
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Receptors, Cytoplasmic and Nuclear
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Receptors, LDL
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Transcription Factors
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farnesoid X-activated receptor
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Chenodeoxycholic Acid
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PCSK9 protein, human
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Proprotein Convertase 9
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Proprotein Convertases
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Serine Endopeptidases
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Pravastatin
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GW 4064