Passive immunization with hypochlorite-oxLDL specific antibodies reduces plaque volume in LDL receptor-deficient mice

PLoS One. 2013 Jul 16;8(7):e68039. doi: 10.1371/journal.pone.0068039. Print 2013.

Abstract

Aims: 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.

Methods and 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.

Conclusion: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology
  • Antibodies, Monoclonal / therapeutic use*
  • Atherosclerosis / prevention & control
  • Immunoglobulin M / immunology
  • Immunoglobulin M / therapeutic use
  • Lipoproteins, LDL / antagonists & inhibitors*
  • Lipoproteins, LDL / immunology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Receptors, LDL / deficiency*

Substances

  • Antibodies, Monoclonal
  • Immunoglobulin M
  • Lipoproteins, LDL
  • Receptors, LDL
  • oxidized low density lipoprotein

Grant support

This research was funded by the transnational University Limburg (tUL). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.