20.500.12556/DiRROS-29183 Proprotein convertase subtilisin/kexin type 9–CC-motif chemokine ligand 2 interactions link lipoprotein(a) composition to intermediate monocyte inflammation in coronary artery disease 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. PCSK9 Lp(a) monocytes (monociti) true false true Angleški jezik Ni določen Neznano 2026-04-23 11:03:06 2026-04-23 11:03:07 2026-04-24 04:05:29 0000-00-00 00:00:00 2026 0 0 Nasl. z nasl. zaslona; Opis vira z dne 14. 4. 2026; 9 str. [article no.] ǂ100563 Vol. 65 2026 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616.13-004.6 2667-0895 10.1016/j.athplu.2026.100563 275117827 RAZ_Ugovsek_Sabina_2026.pdf RAZ_Ugovsek_Sabina_2026.pdf 1 D26C31678592548A9767383A3DC9EB6D 06fc959015cfc604ff069944400b38d50b7648322cafbc2a707b3ef1f11318f7 6d02294b-3ef3-11f1-b867-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43627 https://www.sciencedirect.com/science/article/pii/S2667089526000179?via%3Dihub 1 408c1b54-3ef3-11f1-b867-001a4af901a5 https://dirros.openscience.si/Dokument.php?lang=slv&id=43626 Univerzitetni klinični center Ljubljana 0 0 0