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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Hörl, G; Froehlich, H; Ferstl, U; Ledinski, G; Binder, J; Cvirn, G; Stojakovic, T; Trauner, M; Koidl, C; Tafeit, E; Amrein, K; Scharnagl, H; Jürgens, G; Hallström, S.
Simvastatin Efficiently Lowers Small LDL-IgG Immune Complex Levels: A Therapeutic Quality beyond the Lipid-Lowering Effect.
PLoS One. 2016; 11(2):e0148210-e0148210 Doi: 10.1371/journal.pone.0148210 [OPEN ACCESS]
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Führende Autor*innen der Med Uni Graz
Fröhlich Harald
Hörl Gerd
Co-Autor*innen der Med Uni Graz
Amrein Karin
Binder Josepha Stephanie
Cvirn Gerhard
Ferstl Ulrika
Hallström Seth
Jürgens Günther
Koidl Christoph
Ledinski Gerhard
Scharnagl Hubert
Stojakovic Tatjana
Tafeit Erwin
Trauner Michael

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We investigated a polyethylene glycol non-precipitable low-density lipoprotein (LDL) subfraction targeted by IgG and the influence of statin therapy on plasma levels of these small LDL-IgG-immune complexes (LDL-IgG-IC). LDL-subfractions were isolated from 6 atherosclerotic subjects and 3 healthy individuals utilizing iodixanol density gradient ultracentrifugation. Cholesterol, apoB and malondialdehyde (MDA) levels were determined in each fraction by enzymatic testing, dissociation-enhanced lanthanide fluorescence immunoassay and high-performance liquid chromatography, respectively. The levels of LDL-IgG-IC were quantified densitometrically following lipid electrophoresis, particle size distribution was assessed with dynamic light scattering and size exclusion chromatography. The influence of simvastatin (40 mg/day for three months) on small LDL-IgG-IC levels and their distribution among LDL-subfractions (salt gradient separation) were investigated in 11 patients with confirmed coronary artery disease (CAD). We demonstrate that the investigated LDL-IgG-IC are small particles present in atherosclerotic patients and healthy subjects. In vitro assembly of LDL-IgG-IC resulted in particle density shifts indicating a composition of one single molecule of IgG per LDL particle. Normalization on cholesterol levels revealed MDA values twice as high for LDL-subfractions rich in small LDL-IgG-IC if compared to dominant LDL-subfractions. Reactivity of affinity purified small LDL-IgG-IC to monoclonal antibody OB/04 indicates a high degree of modified apoB and oxidative modification. Simvastatin therapy studied in the CAD patients significantly lowered LDL levels and to an even higher extent, small LDL-IgG-IC levels without affecting their distribution. In conclusion simvastatin lowers levels of small LDL-IgG-IC more effectively than LDL-cholesterol and LDL-apoB levels in atherosclerotic patients. This antiatherogenic effect may additionally contribute to the known beneficial effects of this drug in the treatment of atherosclerosis.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Aged -
Aged, 80 and over -
Antigen-Antibody Complex - blood
Apolipoproteins B - blood
Cholesterol, LDL - blood
Coronary Artery Disease - blood
Coronary Restenosis - blood
Female -
Humans -
Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use
Immunoglobulin G - blood
Male -
Malondialdehyde - blood
Middle Aged -
Peripheral Arterial Disease - blood
Simvastatin - therapeutic use

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