Proprotein convertase subtilisin/kexin type 9–CC-motif chemokine ligand 2 interactions link lipoprotein(a) composition to intermediate monocyte inflammation in coronary artery disease

Ugovšek, Sabina (author), Rehberger Likozar, Andreja (author), Levstek, Tina (author), Trebušak Podkrajšek, Katarina (author), Zupan, Janja (author), Marka, Frieda (author), Trimmel, Tamara (author), Brekalo, Mira (author), Speidl, Walter (author), Hohensinner, Philipp (author), Haider, Patrick (author), Šebeštjen, Miran (author)

Background: Intermediate monocytes (IM) exhibit proinflammatory properties and contribute to atherosclerosis. Elevated lipoprotein(a) [Lp(a)] levels modulate monocyte behavior, while proprotein convertase subtilisin/kexin type 9 (PCSK9) has been implicated in inflammatory pathways beyond lipid metabolism. The effects of PCSK9 inhibition on monocyte subset distribution in high-risk coronary artery disease patients remain unclear. Objective: To assess the effects of lipoprotein fractions and PCSK9 inhibitor (PCSK9i) therapy on monocyte subset distribution in patients with stable coronary artery disease and highly elevated Lp(a) levels. Methods: We followed 100 statin-treated patients in the stable phase after myocardial infarction with highly elevated Lp(a), randomized to PCSK9i or placebo for six months. Biochemical, genetic, and cellular analyses were performed at baseline and follow-up. Results: At baseline, IM levels correlated with total cholesterol (ρ = − 0.202, p = 0.044), triglycerides (ρ = − 0.324, p < 0.001), apolipoprotein A1 (ρ = 0.241, p = 0.016), and PCSK9 concentrations (ρ = − 0.282, p = 0.006). PCSK9 levels were positively associated with CC-motif chemokine ligand 2 (CCL2) (ρ = 0.298, p = 0.005), a marker of monocyte recruitment. PCSK9i therapy did not alter monocyte subset distribution. After treatment, only the association between IM and Lp(a) remained significant (ρ = − 0.258, p = 0.041). KIV-2 repeat number inversely correlated with CCL2 levels (ρ = − 0.319, p = 0.011). Conclusion: In high-risk patients, PCSK9 inhibition modulates monocyte–lipoprotein interactions without affecting the monocyte subset distribution. PCSK9 may promote vascular inflammation through CCL2 regulation, which appears more closely related to Lp(a) composition than its circulating concentration.

• Language: English
• Keywords: PCSK9, Lp(a), monocytes (monociti)
• Work type: Article
• Typology: 1.01 - Original Scientific Article
• Organization: MF - Faculty of Medicine; FFA - Faculty of Pharmacy
• Publication status: Published
• Publication version: Version of Record
• Year: 2026
• Number of pages: 9 str.
• Numbering: Vol. 65, art. 100563
• PID: 20.500.12556/RUL-184318
• UDC: 616.13-004.6
• ISSN on article: 2667-0895
• DOI: 10.1016/j.athplu.2026.100563
• COBISS.SI-ID: 275117827
• Publication date in RUL: 03.07.2026

Record is a part of a journal

• Title: Atherosclerosis plus
• Publisher: Elsevier
• ISSN: 2667-0895
• COBISS.SI-ID: 103569411

Licences

• License: CC BY-NC-ND 4.0, Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
• Link: http://creativecommons.org/licenses/by-nc-nd/4.0/
• Description: The most restrictive Creative Commons license. This only allows people to download and share the work for no commercial gain and for no other purposes.