Multiplex Protein Biomarker Profiling in Patients with Familial Hypercholesterolemia.
Dana DlouhaMilan BlahaEva RohlovaJaroslav Alois HubacekVera LanskaJakub VisekVladimír BlahaPublished in: Genes (2021)
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.
Keyphrases
- low density lipoprotein
- cardiovascular disease
- end stage renal disease
- newly diagnosed
- chronic kidney disease
- ejection fraction
- stem cells
- rheumatoid arthritis
- high fat diet
- coronary artery disease
- cardiovascular events
- gene expression
- adipose tissue
- small molecule
- systemic sclerosis
- disease activity
- cell therapy
- ankylosing spondylitis
- smoking cessation
- genome wide analysis