Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
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
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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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- Abstract:
- 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