Multiplex Protein Biomarker Profiling in Patients with Familial Hypercholesterolemia

• Published in: Genes 2021-10, Vol.12 (10), p.1599
• Main Authors: Dlouha, Dana, Blaha, Milan, Rohlova, Eva, Hubacek, Jaroslav A, Lanska, Vera, Visek, Jakub, Blaha, Vladimir
• Format: Article
• Language: English
• Subjects: Adsorption; Adult; Aged; Anticholesteremic Agents - therapeutic use; Apheresis; Apolipoprotein E; Apolipoproteins; Automation; Biomarkers; Biomarkers - blood; Blood; Blood Proteins - classification; Blood Proteins - genetics; Blood Proteins - isolation & purification; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - blood; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - genetics; Cardiovascular Diseases - pathology; CCL3 protein; CD4 antigen; Cholesterol; Cholesterol - blood; Cholesterol - metabolism; Collagen (type I); Dkk1 protein; Drug therapy; Female; Genes; Hereditary diseases; High density lipoprotein; Humans; Hypercholesterolemia; Hyperlipoproteinemia Type II - blood; Hyperlipoproteinemia Type II - drug therapy; Hyperlipoproteinemia Type II - genetics; Hyperlipoproteinemia Type II - pathology; Inflammation - blood; Inflammation - genetics; Inflammation - metabolism; Interleukin 1; Interleukin 18; Interleukin 27; Lipid metabolism; Lipids; Low density lipoprotein; Low density lipoprotein receptors; Male; Middle Aged; Mutation; Patients; Plasma; Plasma levels; Plasma proteins; Platelet-derived growth factor; Protein expression; Proteins; Tumor necrosis factor receptors
• ISSN: 2073-4425; 2073-4425
• DOI: 10.3390/genes12101599

Familial hypercholesterolemia (FH), is an autosomal dominant disorder caused by mutations in the , , , and 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 ( = 18; men = 8, age 55.4 ± 13.1 years) and patients under combined long-term LDL apheresis/hypolipidemic therapy ( = 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 < 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 < 0.006). Hypolipidemic treatment mainly affected biomarkers involved in vascular endothelial maintenance. Combined therapy influenced proteins that participate in cholesterol metabolism and inflammation.