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Updated: May 17, 2026
Quantitative Analysis and Characterization of Atherosclerotic Lesions in the Murine Aortic Sinus
Published on: December 7, 2013
PCSK9 expression in human atherosclerotic lesions and vascular smooth muscle cells
Yara Azar1, Yara Abou Khalil1, Marie-Nathalie Lebel2
1Paris Cité University and Sorbonne Paris Nord University, INSERM UMRS 1148, Laboratory for Vascular Translational Science (LVTS), Paris, France; Saint-JosephUniversity of Beirut, Faculty of Pharmacy, Pôle Technologies-Santé (PTS), Laboratory of Biochemistry and Molecular Therapeutics (LBTM), Beirut, Lebanon.
Insights
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is found in human atherosclerotic lesions, not synthesized locally. Vascular smooth muscle cells internalize PCSK9 via LDL receptor-related protein 1 (LRP1).
Area of Science:
- Cardiovascular Biology
- Atherosclerosis Research
- Molecular Medicine
Background:
- Proprotein convertase subtilisin/kexin type 9 (PCSK9) is crucial in cholesterol regulation and linked to atherosclerosis.
- While PCSK9's role in hepatocytes is known, its direct interaction with arterial pathology requires elucidation.
- Vascular smooth muscle cells (vSMC) are key players in arterial wall pathophysiology.
Purpose of the Study:
- To investigate the presence and localization of PCSK9 in human atherosclerotic lesions.
- To explore the interaction between PCSK9 and vSMC in the context of arterial pathology.
Main Methods:
- Collection and fixation of healthy and atheromatous human aortas.
- Isolation of primary vSMC from aortic media.
- Analysis of PCSK9 presence, gene expression, and uptake by vSMC, including investigation of LRP1 involvement.
Main Results:
- PCSK9 was present in human atherosclerotic tissues, particularly in foam cells, but rare in healthy tissues.
- PCSK9 is not synthesized by vSMC but can be internalized by them.
- PCSK9 uptake by vSMC occurs via LDL receptor-related protein 1 (LRP1) and competes with oxidized LDL uptake.
Conclusions:
- PCSK9 is present in the aortic wall of atherosclerotic patients but not locally synthesized.
- Vascular smooth muscle cells internalize PCSK9 through LRP1, suggesting a novel mechanism in arterial pathology.
Aims:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the third gene involved in autosomal dominant hypercholesterolemia, an atherosclerosis major cause. Its role in regulating plasma cholesterol through hepatocyte functions has been widely reported, and anti-PCSK9 drugs have been developed. However, direct interactions between PCSK9 and arterial pathology are not fully elucidated. As vascular smooth muscle cells (vSMC) play a major role in arterial wall pathophysiology, we describe PCSK9's presence in human atherosclerotic lesions and its interaction with vSMC.
Methods:
Healthy and atheromatous human aortas were collected, tissues fixed, and tissue soluble release obtained after 24 h incubation in serum-free medium. Primary vSMC were isolated from aortic media.
Results:
We showed that PCSK9, though rare in healthy tissues, was present in fibroatheromas and fatty streaks, and localized in foam cells. PCSK9 gene expression was low in the arterial wall, and no PCSK9 protein was detected in primary vSMC. However, primary vSMC could uptake PCSK9. Moreover, PCSK9 and oxidized LDL (ox-LDL) uptakes were reciprocally reduced, suggesting competition to enter vSMC. LDL receptor-related protein 1 (LRP1), a known ox-LDL receptor and potential PCSK9 receptor, had its gene expression highly expressed in primary vSMC. An LRP1-ligand antagonist significantly decreased PCSK9 uptake by vSMC. The PCSK9 monoclonal antibody reduced PCSK9 uptake by vSMC in a concentration-dependent manner.
Conclusions:
We characterized the presence of PCSK9 in healthy and atherosclerotic human tissues and demonstrated that PCSK9 present in the aortic wall is not synthesized locally. Our results suggest that vSMC is internalizing PCSK9 through LRP1.
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