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 important 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 factor-A (VEGF-A) (VEGFA), and coagulation and fibrinolysis markers tissue factor (TF) (F3) and plasminogen 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.

Immune-Related Genes and Immune Cell Infiltration Characterize the Maturation Status of Arteriovenous Fistulas: An Integrative Bioinformatics Study and Experimental Validation Based on Transcriptome Sequencing

“…It may be a viable treatment option to use PCSK9 inhibitors, which have a cardiovascular protective effect, to promote VEGFA expression while mitigating the pro-inflammatory effects of high IL1B. 33,34 Further studies are needed to confirm the role of IL1B in the maturation of arteriovenous fistula.…”

Lipoprotein(a) as a Risk Factor for Cardiovascular Diseases: Pathophysiology and Treatment Perspectives

“…Lp(a) is an important carrier of oxidized phospholipids (OxPL) that may play a key role in the process [ 96 ]. Moreover, Lp(a) may favor the onset and development of CAVD by causing aortic valve endothelial dysfunction, accumulating in the valve, and delivering its OxPL content along with autotaxin (ATX) [ 97 ]. This mechanism promotes not only inflammation but also the osteogenic transformation of valvular interstitial cells causing calcium deposition [ 98 ].…”

Competing Endogenous RNA Regulatory Networks of hsa_circ_0126672 in Pathophysiology of Coronary Heart Disease

“…Gene expression profiles have reflected pathological states in several disorders, e.g., cancer [ 9 ], chronic kidney disease (CKD) [ 10 ], metabolic syndrome [ 11 ], and CHD [ 12 ]. Scientific investigation indicates the gradual changes in gene expression profile during the development of CHD [ 12 ].…”

“…Gene expression profiles have reflected pathological states in several disorders, e.g., cancer [ 9 ], chronic kidney disease (CKD) [ 10 ], metabolic syndrome [ 11 ], and CHD [ 12 ]. Scientific investigation indicates the gradual changes in gene expression profile during the development of CHD [ 12 ]. The use of gene expression signatures to discover CHD biomarkers for diagnosis, treatment, prognosis, and monitoring of the disease has yielded promising results [ 13 , 14 ].…”