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Published on: November 17, 2018
PCSK9 Inhibitors Reduce Oxidative Stress Biomarkers in Heterozygous Familial Hypercholesterolemia
Agnieszka Woźniak-Szczepocka1, Agnieszka Pawlos1, Paulina Gorzelak-Pabiś1
1Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Lodz, Poland.
Journal of Cellular and Molecular Medicine
|May 25, 2026
Summary
PCSK9 inhibitors significantly reduce oxidative stress and DNA damage in patients with heterozygous familial hypercholesterolemia (HeFH). This therapy offers non-lipid benefits, supporting its role in preventing atherosclerosis.
Area of Science:
- Cardiovascular Medicine
- Biochemistry
Background:
- Heterozygous familial hypercholesterolemia (HeFH) is characterized by elevated LDL-C and increased oxidative stress, promoting atherosclerosis.
- Oxidative stress in HeFH contributes to LDL oxidation (ox-LDL), DNA damage, and reduced antioxidant capacity.
Purpose of the Study:
- To evaluate the impact of Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors on oxidative stress and DNA damage in HeFH patients.
- To assess reductions in ox-LDL, anti-ox-LDL antibodies, oxidative stress markers (e.g., 8-OHdG), and DNA damage levels.
Main Methods:
- A study involving 40 HeFH patients and 33 healthy controls.
- Analysis of lipid profiles, Lp(a), ox-LDL, anti-ox-LDL antibodies, plasma antioxidant capacity (TAC), and DNA damage (comet assay).
- Treatment group received PCSK9 inhibitors (alirocumab or evolocumab).
Main Results:
- PCSK9 inhibitor treatment significantly improved lipid profiles in HeFH patients.
- Therapy reduced oxidative stress markers (8-OHdG, ox-LDL) and increased anti-ox-LDL antibodies and TAC.
- Significant reduction in purine and pyrimidine DNA damage was observed, with greater efficacy noted for alirocumab.
Conclusions:
- PCSK9 inhibitors provide significant non-lipid benefits by reducing oxidative stress and DNA damage in HeFH.
- These findings support the use of PCSK9 inhibitors for preventing atherosclerotic complications beyond LDL-C reduction.
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