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


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.
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.
Kuang-Yuh
KY
Chyu
Odette S
OS
Reyes
Xiaoning
X
Zhao
Juliana
J
Yano
Paul
P
Dimayuga
Jan
J
Nilsson
Bojan
B
Cercek
Prediman K
PK
Shah
D000818:Animals; D000917:Antibody Formation; D001011:Aorta / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D008078:Cholesterol, LDL / Q000097:blood / Q000276:immunology*; D006937:Hypercholesterolemia / Q000276:immunology / Q000628:therapy; D007111:Immunity, Cellular; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood; D008077:Lipoproteins, LDL / Q000097:blood / Q000276:immunology; D008297:Male; D051379:Mice; D018345:Mice, Knockout
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D007074:Immunoglobulin G; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein