title: Carbamyl adducts on low-density lipoprotein induce IgG response in LDLR-/- mice and bind plasma autoantibodies in humans under enhanced carbamylation.
abstract: OBJECTIVE
  Post-translational modification of proteins via carbamylation predicts increased risk for coronary artery disease. Uremia and smoke exposure are known to increase carbamylation. The aim was to investigate the role of carbamylated low-density lipoprotein (LDL) immunization on antibody formation and atherogenesis in LDL receptor-deficient (LDLR-/-) mice, and to study autoantibodies to carbamylated proteins in humans with carbamylative load.
  
  
  RESULTS
  LDLR-/- mice immunized with carbamylated mouse LDL (msLDL; n=10) without adjuvant showed specific immunoglobulin G (IgG) antibody levels to carbamyl-LDL and malondialdehyde-modified LDL (MDA-LDL) but not to oxidized LDL or native LDL. Immunization did not influence the atherosclerotic plaque area compared with control LDLR-/- mice immunized with native msLDL (n=10) or phosphate-buffered saline (n=11). Humans with high plasma urea levels, as well as smokers, had increased IgG autoantibody levels to carbamyl-modified proteins compared to the subjects with normal plasma urea levels, or to nonsmokers.
  
  
  METHODS
  Carbamyl-LDL induced specific IgG antibody response cross-reactive with MDA-LDL in mice. IgG antibodies to carbamyl-LDL were also found in human plasma and related to conditions known to have increased carbamylation, such as uremia and smoking. Plasma antibodies to carbamylated proteins may serve as new indicator of in vivo carbamylation.
  
  
  CONCLUSIONS
  These data give insight into mechanisms of in vivo humoral recognition of post-translationally modified structures. Humoral IgG immune response to carbamylated proteins is suggested to play a role in conditions leading to enhanced carbamylation, such as uremia and smoking.
authors: 1 Department of Medical Microbiology & Immunology, Institute of Diagnostics, University of Oulu , Oulu, Finland .
authors: Outi
authors: O
authors: Kummu
authors: S Pauliina
authors: SP
authors: Turunen
authors: Chunguang
authors: C
authors: Wang
authors: Jaakko
authors: J
authors: Lehtimäki
authors: Marja
authors: M
authors: Veneskoski
authors: Helena
authors: H
authors: Kastarinen
authors: Marja-Kaisa
authors: MK
authors: Koivula
authors: Juha
authors: J
authors: Risteli
authors: Y Antero
authors: YA
authors: Kesäniemi
authors: Sohvi
authors: S
authors: Hörkkö
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000097:blood / Q000235:genetics / Q000473:pathology; D001323:Autoantibodies / Q000097:blood*; D003324:Coronary Artery Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008315:Malondialdehyde / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011973:Receptors, LDL / Q000235:genetics
chemical_list: D001323:Autoantibodies; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C039916:carbamyl-LDL; D008315:Malondialdehyde