PCSK9 expression in human atherosclerotic lesions and vascular smooth muscle cells.

作者：Y. Azar, Yara Abou Khalil, M. Lebel, Y. Ghaleb, S. El Bitar, Gaelle Merheb, C. Deschildre, Hugo Le Bon, S. Dupont, I. Guillas, Wilfried Le Goff, Catherine Boileau, Marianne Abifadel, Jean-Baptiste Michel, P. El Khoury, M. Varret · 发表于：Atherosclerosis · 年份：2026 · DOI：10.1016/j.atherosclerosis.2026.120696 · 被引用次数：1 · 研究领域：Medicine

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 manne...