Journal
ATHEROSCLEROSIS
Volume 201, Issue 2, Pages 266-273Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2008.02.004
Keywords
HepG2; PCSK9; LDLR; Berberine
Funding
- Rikshospitalet University Hospital
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Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) post-transcriptionally downregulates the low-density lipoprotein receptor (LDLR) by binding to the receptor's epidermal growth factor repeat A on the cell surface and shuttling the LDLR to the lysosomes for deoradation. Mutations in the PCSK9 gene have been shown to cause either hypo- or hypercholesterolemia. Here we investigated the effect of berberine, a natural plant extract. on PCSK9 expression in HepG2 cells. Results: Berberine decreases PCSK9 mRNA and protein levels in a time- and dose-dependent manner. This was not due to increased degradation of PCSK9 mRNA but most likely due to a decreased transcription of the PCSK9 gene. We also show that a combination of berberine and mevastatin increases LDLR mRNA and protein levels, while suppressing the increase in PCSK9 mRNA levels caused by mevastatin alone. Conclusion: Berberine may be a useful supplement to statin treatment due to its effects on PCSK9 mRNA and protein levels. (C) 2008 Elsevier Ireland Ltd. All rights reserved.
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