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A High-Throughput Luciferase Assay to Evaluate Proteolysis of the Single-Turnover Protease PCSK9
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Effect of PCSK9 Inhibitors on Regulators of Lipoprotein Homeostasis, Inflammation and Coagulation

Patricija Lunar1, Hana Meglič1, Mateja Vehar2

  • 1Faculty of Medicine, University of Ljubljana, Vrazov trg 2, 1000 Ljubljana, Slovenia.

Biomedicines
|February 26, 2025
PubMed

Insights

PCSK9 inhibitors significantly alter gene expression related to lipid regulation, inflammation, and coagulation in coronary artery disease patients. This suggests PCSK9i impacts atherosclerosis beyond just lowering lipids.

Area of Science:

  • Cardiovascular Medicine
  • Molecular Biology
  • Pharmacogenomics

Background:

  • Atherosclerosis involves inflammation and haemostasis.
  • PCSK9 inhibitors (PCSK9i) are emerging atherosclerosis treatments.
  • Investigating PCSK9i effects on gene expression in CAD patients.

Purpose of the Study:

  • To assess PCSK9i influence on gene expression in CAD patients.
  • To examine regulators of lipoprotein homeostasis, inflammation, and coagulation.

Main Methods:

  • Quantitative polymerase chain reaction (qPCR) used for gene expression analysis.
  • Studied genes: SREBP1, SREBP2, LDLR, LIPC, LRP8, CD36, CD63, CD14.
  • Analysis included 96 CAD patients and 25 healthy controls.

Main Results:

  • Significant differences in gene expression between CAD patients and healthy controls.
  • PCSK9i treatment led to significant changes in all studied genes' expression.
  • Gene expression alterations occurred in lipid regulators, inflammatory markers, and coagulation parameters.

Conclusions:

  • PCSK9 inhibitors significantly affect gene expression of lipid regulators.
  • PCSK9i also impact inflammatory markers and coagulation parameters.
  • These effects appear independent of PCSK9i's lipolytic activity.
Abstract

Keywords:
PCSK9 inhibitorscoagulationcoronary artery diseaseinflammationlipid regulators

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