title: Passive immunization with hypochlorite-oxLDL specific antibodies reduces plaque volume in LDL receptor-deficient mice.
abstract: OBJECTIVE
  New strategies to overcome complications of cardiovascular diseases are needed. Since it has been demonstrated that atherosclerosis is an inflammatory disease, modulation of the immune system may be a promising approach. Previously, it was suggested that antibodies may confer protective effects on the development of atherosclerosis. In this study, we hypothesised that passive immunization with anti-oxLDL IgM antibodies specific for hypochlorite (HOCl) may be athero-protective in mice.
  
  
  RESULTS
  Monoclonal mouse IgM antibodies were produced and the antibody with specificity for hypochlorite-oxLDL (HOCl-oxLDL) (Moab A7S8) was selected. VH sequence determination revealed that Moab A7S8 is a natural IgM antibody. Atherosclerosis in LDLr(-/-) mice was induced by a perivascular collar placement around the right carotid artery in combination with feeding a high-fat diet. Subsequently, the mice were treated every six days with 500 µg Moab A7S8, non-relevant IgM or with PBS and the carotid arteries and aortic roots were studied for atherosclerosis. Passive immunization with this Moab A7S8 resulted in a significant reduced plaque volume formation in LDLr(-/-) mice when compared with PBS treatment (P = 0.002 and P = 0.035). Cholesterol levels decreased by 20% when mice were treated with Moab A7S8 compared to PBS. Furthermore, anti-oxLDL specific IgM and IgG antibody production increased significantly in the Moab A7S8 treated mice in comparison with PBS treated mice.
  
  
  CONCLUSIONS
  Our data show that passive immunization with a natural IgM antibody, directed to HOCl-oxLDL, can reduce atherosclerotic plaque development. We postulate that specific antibody therapy may be developed for use in human cardiovascular diseases.
authors.affiliation: Internal Medicine, Clinical and Experimental Immunology, Cardiovascular Research Institute Maastricht, Maastricht University Medical Center, Maastricht, The Netherlands.
authors.forename: Marcella
authors.initials: M
authors.lastname: van Leeuwen
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Kemna
authors.forename: Menno P J
authors.initials: MP
authors.lastname: de Winther
authors.forename: Louis
authors.initials: L
authors.lastname: Boon
authors.forename: Adriaan M
authors.initials: AM
authors.lastname: Duijvestijn
authors.forename: Darius
authors.initials: D
authors.lastname: Henatsch
authors.forename: Nico A
authors.initials: NA
authors.lastname: Bos
authors.forename: Marion J J
authors.initials: MJ
authors.lastname: Gijbels
authors.forename: Jan Willem Cohen
authors.initials: JW
authors.lastname: Tervaert
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000517:prevention & control; D007075:Immunoglobulin M / Q000276:immunology / Q000627:therapeutic use; D008077:Lipoproteins, LDL / Q000037:antagonists & inhibitors* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency*
chemical_list: D000911:Antibodies, Monoclonal; D007075:Immunoglobulin M; D008077:Lipoproteins, LDL; D011973:Receptors, LDL; C099252:oxidized low density lipoprotein