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

Chyu, Kuang-Yuh; Reyes, Odette S; Zhao, Xiaoning; Yano, Juliana; Dimayuga, Paul; Nilsson, Jan; Cercek, Bojan; Shah, Prediman K

doi:10.1016/j.atherosclerosis.2004.04.016

« Previous Next »Atherosclerosis
Volume 176, Issue 1 , Pages 27-35, September 2004

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

Kuang-Yuh Chyu
- Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA
Odette S Reyes
- Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA
Xiaoning Zhao
- Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA
Juliana Yano
- Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA
Paul Dimayuga
- Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA
Jan Nilsson
- Department of Medicine, Lund University, University Hospital MAS, Malmo, Sweden
Bojan Cercek
- Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA
Prediman K Shah
- Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and UCLA School of Medicine, 8700 Beverly Blvd., Los Angeles, CA 90048, USA
- Corresponding author. Present address: Room 5347, 8700 Beverly Blvd, Los Angeles, CA 90048, USA. Tel.: +1 310 423 3884; fax: +1 310 423 0144.

Received 14 May 2003; received in revised form 25 December 2003; accepted 8 April 2004.

Abstract

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.

Keywords: Atherosclerosis, LDL, Immunization