title: Simvastatin Efficiently Lowers Small LDL-IgG Immune Complex Levels: A Therapeutic Quality beyond the Lipid-Lowering Effect.
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.
authors: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors: Gerd
authors: G
authors: Hörl
authors: Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Harald
authors: H
authors: Froehlich
authors: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors: Ulrika
authors: U
authors: Ferstl
authors: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors: Gerhard
authors: G
authors: Ledinski
authors: Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Josepha
authors: J
authors: Binder
authors: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors: Gerhard
authors: G
authors: Cvirn
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors: Tatjana
authors: T
authors: Stojakovic
authors: Division of Gastroenterology and Hepatology, Department of Medicine III, Medical University of Vienna, Vienna, Austria.
authors: Michael
authors: M
authors: Trauner
authors: Institute of Hygiene, Medical University of Graz, Graz, Austria.
authors: Christoph
authors: C
authors: Koidl
authors: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors: Erwin
authors: E
authors: Tafeit
authors: Division of Endocrinology and Metabolism, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
authors: Karin
authors: K
authors: Amrein
authors: Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
authors: Hubert
authors: H
authors: Scharnagl
authors: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors: Günther
authors: G
authors: Jürgens
authors: Institute of Physiological Chemistry, Center of Physiological Medicine, Medical University of Graz, Graz, Austria.
authors: Seth
authors: S
authors: Hallström
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000936:Antigen-Antibody Complex / Q000097:blood* / Q000276:immunology; D001055:Apolipoproteins B / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood / Q000276:immunology; D003324:Coronary Artery Disease / Q000097:blood / Q000188:drug therapy*; D023903:Coronary Restenosis / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D008875:Middle Aged; D058729:Peripheral Arterial Disease / Q000097:blood / Q000188:drug therapy*; D019821:Simvastatin / Q000627:therapeutic use*
chemical_list: D000936:Antigen-Antibody Complex; D001055:Apolipoproteins B; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007074:Immunoglobulin G; D008315:Malondialdehyde; D019821:Simvastatin