New epigenome players in the regulation of PCSK9-H3K4me3 and H3K9ac alterations by statin in hypercholesterolemia
2024

Statins and PCSK9 Regulation

Sample size: 16 publication 10 minutes Evidence: moderate

Author Information

Author(s): Duddu Sushmitha, Katakia Yash T., Chakrabarti Rituparna, Sharma Pooja, Shukla Praphulla Chandra

Primary Institution: Indian Institute of Technology Kharagpur

Hypothesis

Statins modulate the expression of PCSK9 through epigenetic regulation involving histone modifications.

Conclusion

Statins increase PCSK9 expression by enhancing histone methylation and acetylation, which can be reversed by specific inhibitors.

Supporting Evidence

  • Statins increase the expression of PCSK9 by regulating the expression of SREBP2.
  • Treatment with atorvastatin significantly upregulated both transcript and protein levels of PCSK9.
  • Pharmacological inhibition of histone marks reversed the statin-induced upregulation of PCSK9.
  • Combination of statins with specific inhibitors improved LDL uptake in hepatocytes.

Takeaway

Statins help lower bad cholesterol but can also raise a protein called PCSK9 that makes it harder to do so; this study found ways to reduce PCSK9 levels.

Methodology

The study involved in vitro experiments with HepG2 cells and in vivo experiments with mice to assess the effects of atorvastatin on PCSK9 expression and histone modifications.

Potential Biases

Potential bias in the interpretation of results due to reliance on specific animal models and cell lines.

Limitations

The study primarily focused on in vitro and animal models, limiting direct applicability to human patients.

Participant Demographics

Male C57BL6 mice aged 6-8 weeks were used in the study.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1016/j.jlr.2024.100699

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