Familial hypercholesterolemia (FH), is an autosomal dominant disorder caused by mutations in the LDLR, APOB, PCSK9, and APOE genes and is characterized by high plasma levels of total and low-density lipoprotein (LDL) cholesterol. Our study aimed to analyze the influences of two different therapies on a wide spectrum of plasma protein biomarkers of cardiovascular diseases. Plasma from FH patients under hypolipidemic therapy (N = 18; men = 8, age 55.4 ± 13.1 years) and patients under combined long-term LDL apheresis/hypolipidemic therapy (N = 14; men = 7; age 58.0 ± 13.6 years) were analyzed in our study. We measured a profile of 184 cardiovascular disease (CVD) associated proteins using a proximity extension assay (PEA). Hypolipidemic therapy significantly (all p < 0.01) influenced 10 plasma proteins (TM, DKK1, CCL3, CD4, PDGF subunit B, AGRP, IL18, THPO, and LOX1 decreased; ST2 increased). Under combined apheresis/hypolipidemic treatment, 18 plasma proteins (LDLR, PCSK9, MMP-3, GDF2, CTRC, SORT1, VEGFD, IL27, CCL24, and KIM1 decreased; OPN, COL1A1, KLK6, IL4RA, PLC, TNFR1, GLO1, and PTX3 increased) were significantly affected (all p < 0.006). Hypolipidemic treatment mainly affected biomarkers involved in vascular endothelial maintenance. Combined therapy influenced proteins that participate in cholesterol metabolism and inflammation.

1st Faculty of Medicine Charles University 128 00 Prague Czech Republic

3rd Department of Internal Medicine Metabolism and Gerontology Faculty of Medicine in Hradec Králové University Hospital Hradec Králové and Charles University 500 05 Hradec Králové Czech Republic

4th Department of Internal Medicine Hematology Faculty of Medicine in Hradec Králové University Hospital Hradec Králové and Charles University 500 05 Hradec Králové Czech Republic

Center for Experimental Medicine Institute for Clinical and Experimental Medicine Videnska 1958 9 140 21 Prague Czech Republic

Department of Anthropology and Human Genetics Faculty of Science Charles University 120 00 Prague Czech Republic

Laboratory of Gene Expression Institute of Biotechnology CAS BIOCEV 252 50 Vestec Czech Republic

Statistical Unit Institute for Clinical and Experimental Medicine 140 21 Prague Czech Republic

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