Gene Expression Profiling of Markers of Inflammation, Angiogenesis, Coagulation and Fibrinolysis in Patients with Coronary Artery Disease with Very High Lipoprotein(a) Levels Treated with PCSK9 Inhibitors

Abstract

Besides lipids, inflammation, angiogenesis, coagulation and fibrinolysis play very im-portant roles in coronary artery disease (CAD). We measured gene expression of the inflammatory markers interleukin (IL)-1β (IL1B) and interferon (IFN)-γ (IFNG), vascular endothelial growth fac-tor-A (VEGF-A) (VEGFA), and coagulation and fibrinolysis markers tissue factor (TF) (F3) and plas-minogen activator inhibitor-1 (PAI-1) (SERPINE) in healthy controls and CAD patients with high lipoprotein(a) (Lp(a)). The aim of our study was to identify, first, if there is a difference in these markers between controls and patients; secondly, if these markers are associated with lipids; and third, what the influence of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors is on these markers. We included 124 subjects, 27 controls and 97 patients with CAD (30 in placebo and 67 in the PCSK9 group). Blood samples were collected for lipid and gene measurement. The results showed higher expression of IL1B (p < 0.0001), VEGFA (p < 0.0001), and F3 (p = 0.018) in controls in comparison with patients. Significant correlations were observed between IL1B and lipids. Treatment with PCSK9 inhibitors increased VEGFA (p < 0.0001) and F3 (p = 0.001), and decreased SERPINE (p = 0.043). The results of our study underpin the importance of IL-1β, VEGF-A and TF in CAD as well as the effect of PCSK9 treatment on these markers.