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.
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.
Authors: Kuang-Yuh Chyu; Xiaoning Zhao; Paul C Dimayuga; Jianchang Zhou; Xiaojun Li; Juliana Yano; Wai Man Lio; Lai Fan Chan; Jonathan Kirzner; Portia Trinidad; Bojan Cercek; Prediman K Shah Journal: PLoS One Date: 2012-02-09 Impact factor: 3.240
Authors: Paul C Dimayuga; Xiaoning Zhao; Juliana Yano; Wai Man Lio; Jianchang Zhou; Peter M Mihailovic; Bojan Cercek; Prediman K Shah; Kuang-Yuh Chyu Journal: J Am Heart Assoc Date: 2017-07-15 Impact factor: 5.501
Authors: Kuang-Yuh Chyu; Wai Man Lio; Paul C Dimayuga; Jianchang Zhou; Xiaoning Zhao; Juliana Yano; Portia Trinidad; Tomoyuki Honjo; Bojan Cercek; Prediman K Shah Journal: PLoS One Date: 2014-03-19 Impact factor: 3.240