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Updated: Aug 27, 2025
08:14
A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
Published on: August 28, 2018
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Irisin inhibits PCSK9 expression through activating AMPK-SREBP2 pathway
Runqiu Xu1, Qi Liu1, Xiaoxue Ma1
1The Key Laboratory of Myocardial Ischemia Organization, Chinese Ministry of Education, Harbin, Heilongjiang, 150086, China; Department of Cardiology Organization, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150086, China.
Biochemical and Biophysical Research Communications
|September 24, 2022
Summary
Irisin reduces proprotein convertase subtilisin/kexin type 9 (PCSK9) and inflammation in cells exposed to oxidized low-density lipoprotein (ox-LDL). This effect is mediated by the AMP-dependent protein kinase (AMPK)-sterol-regulatory element binding protein 2 (SREBP2) pathway.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Cellular Inflammation
Background:
- Oxidized low-density lipoprotein (ox-LDL) induces vascular wall inflammation.
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) contributes to vascular inflammation.
- The interaction between irisin and PCSK9 in vascular cells is not well understood.
Purpose of the Study:
- To investigate the effect of irisin on PCSK9 expression in endothelial cells and hepatocytes.
- To explore the role of the AMP-dependent protein kinase (AMPK) and sterol-regulatory element binding protein 2 (SREBP2) pathway in this interaction.
- To determine how irisin influences ox-LDL-induced inflammation via PCSK9.
Main Methods:
- Human umbilical vein endothelial cells and Hep G2 cells were treated with irisin and/or ox-LDL.
- Expression levels of PCSK9, inflammatory proteins, p-AMPK, and SREBP2 were analyzed.
- AMPK activation was inhibited using Compound C and silenced using SiAMPK to validate the pathway.
Main Results:
- Irisin significantly downregulated ox-LDL-induced PCSK9 and inflammation-related protein expression.
- Irisin treatment restored p-AMPK levels and reduced SREBP2 content.
- Inhibition or silencing of AMPK weakened the beneficial effects of irisin.
Conclusions:
- Irisin suppresses PCSK9 expression via the AMPK-SREBP2 pathway.
- Irisin ameliorates ox-LDL-induced inflammation in endothelial cells.
- This study elucidates a novel mechanism for irisin's protective role in vascular health.
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