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Timing affects the efficacy of LDL immunization on atherosclerotic lesions in apo E (-/-) mice

  • KY Chyu
  • OS Reyes
  • XN Zhao
  • J Yano
  • P Dimayuga
  • Jan Nilsson
  • B Cercek
  • PK Shah
Publishing year: 2004
Language: English
Pages: 27-35
Publication/Series: Atherosclerosis
Volume: 176
Issue: 1
Document type: Journal article
Publisher: Elsevier
Additional info: The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Emergency medicine/Medicine/Surgery (013240200), Experimental Cardiovascular Research Unit (013242110)

Abstract english

Background: Immunization of animals with LDL reduces atherosclerosis. However, whether the timing of immunization affects its efficacy is not known. In this study, we evaluated the influence of timing of immunization on the athero-protective effects of LDL immunization in apo E (-/-) mice. Methods and results: Hypercholesterolemic apo E (-/-) mice were immunized with native LDL (nLDL) at age of 6-7 weeks old or at 20 weeks old. Compared to adjuvant group, mice that were immunized at the age of 6-7 weeks developed significantly smaller aortic sinus plaques with reduced gelatinolytic activity and increased collagen content. This was associated with an increase of oxidized LDL (oxLDL) antibody titer and a marked decrease in splenic IL-4 mRNA expression. Immunization at 20 weeks of age also increased oxLDL antibody titer but did not reduce plaque size, gelatinolytic activity or collagen content but resulted in a modest decrease in macrophage infiltration. Late immunization did not alter splenic IL-4 mRNA expression. Conclusions: Our findings demonstrate that, only early nLDL immunization modulates humoral and cellular immune responses and affects plaques size and composition in apo E (-/-) mice, indicating the critical importance of timing of immunization for its antiatherogenic efficacy. (C) 2004 Elsevier Ireland Ltd. All rights reserved.


  • Cardiac and Cardiovascular Systems
  • atherosclerosis
  • LDL
  • immunization


  • Cardiovascular Research - Immunity and Atherosclerosis
  • ISSN: 1879-1484
E-mail: jan [dot] nilsson [at] med [dot] lu [dot] se

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