Related Experiment Video
Updated: Aug 5, 2025
Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
Published on: January 28, 2020
PCSK9 Inhibitors Reduce PCSK9 and Early Atherogenic Biomarkers in Stimulated Human Coronary Artery Endothelial Cells
Rahayu Zulkapli1,2,3, Suhaila Abd Muid1,2, Seok Mui Wang1,2
1Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM), Universiti Teknologi MARA (UiTM), Sungai Buloh Campus, Jalan Hospital, Sungai Buloh 47000, Selangor, Malaysia.
Abstract:
Despite reports on the efficacy of proprotein convertase subtilisin-Kexin type 9 (PCSK9) inhibitors as a potent lipid-lowering agent in various large-scale clinical trials, the anti-atherogenic properties of PCSK9 inhibitors in reducing PCSK9 and atherogenesis biomarkers via the NF-ĸB and eNOS pathway has yet to be established. This study aimed to investigate the effects of PCSK9 inhibitors on PCSK9, targeted early atherogenesis biomarkers, and monocyte binding in stimulated human coronary artery endothelial cells (HCAEC). HCAEC were stimulated with lipopolysaccharides (LPS) and incubated with evolocumab and alirocumab. The protein and gene expression of PCSK9, interleukin-6 (IL-6), E-selectin, intercellular adhesion molecule 1 (ICAM-1), nuclear factor kappa B (NF-ĸB) p65, and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. The binding of U937 monocytes to endothelial cell capacity was measured by the Rose Bengal method. The anti-atherogenic effects of evolocumab and alirocumab were contributed to by the downregulation of PCSK9, early atherogenesis biomarkers, and the significant inhibition of monocyte adhesion to the endothelial cells via the NF-ĸB and eNOS pathways. These suggest the beyond cholesterol-lowering beneficial effects of PCSK9 inhibitors in impeding atherogenesis during the initial phase of atherosclerotic plaque development, hence their potential role in preventing atherosclerosis-related complications.
Insights
PCSK9 inhibitors reduce PCSK9 and atherogenesis biomarkers, inhibiting monocyte adhesion via NF-ĸB and eNOS pathways. These findings suggest PCSK9 inhibitors offer benefits beyond lipid-lowering for preventing early atherosclerosis.
Area of Science:
- Cardiovascular Biology
- Molecular Medicine
- Pharmacology
Background:
- Proprotein convertase subtilisin-Kexin type 9 (PCSK9) inhibitors are effective lipid-lowering agents.
- The anti-atherogenic mechanisms of PCSK9 inhibitors, particularly their impact on inflammatory pathways, require further elucidation.
Purpose of the Study:
- To investigate the effects of PCSK9 inhibitors (evolocumab and alirocumab) on PCSK9 levels, atherogenesis biomarkers, and monocyte adhesion.
- To explore the involvement of the nuclear factor kappa B (NF-ĸB) and endothelial nitric oxide synthase (eNOS) pathways in the anti-atherogenic actions of PCSK9 inhibitors.
Main Methods:
- Human coronary artery endothelial cells (HCAEC) were stimulated with lipopolysaccharides (LPS) and treated with PCSK9 inhibitors.
- Protein and gene expression of PCSK9, IL-6, E-selectin, ICAM-1, NF-ĸB p65, and eNOS were quantified.
- Monocyte adhesion to endothelial cells was assessed using the Rose Bengal method.
Main Results:
- PCSK9 inhibitors downregulated PCSK9 and key early atherogenesis biomarkers (IL-6, E-selectin, ICAM-1).
- Significant inhibition of monocyte adhesion to LPS-stimulated HCAEC was observed.
- These effects were mediated through modulation of the NF-ĸB and eNOS pathways.
Conclusions:
- PCSK9 inhibitors exhibit anti-atherogenic properties by reducing PCSK9, inflammatory biomarkers, and monocyte adhesion.
- The findings highlight the role of NF-ĸB and eNOS pathways in the mechanism of action.
- PCSK9 inhibitors possess benefits beyond lipid reduction, potentially impeding early atherogenesis and preventing related complications.
Related Concept Videos
01:30Coronary Artery Disease I: Introduction
01:26Coronary Artery Disease II: Pathophysiology
01:26Coronary Artery Disease IV: Preventive Measures
01:19Blood Studies for Cardiovascular System II: CRP, Hcy, and Cardiac Natriuretic Peptide Markers
These markers indicate stress or strain on the heart muscle:
Natriuretic Peptides (BNP)
Cardiac myocytes produce these hormones in response to ventricular stretching...
01:20Blood Studies for Cardiovascular System I: Cardiac Biomarkers
The essential diagnostic tools for detecting myocardial necrosis and monitoring individuals suspected of having acute coronary syndrome (ACS) include:
Troponins
Troponins, particularly cardiac troponins I and T, are the most precise and sensitive markers of myocardial injury. They are detectable within 4-6 hours of myocardial injury and remain...
01:30Atherosclerosis I: Introduction