Immunization using an Apo B-100 related epitope reduces atherosclerosis and plaque inflammation in hypercholesterolemic apo E (-/-) mice.
Immune system modulates atherosclerosis and immunization using homologous LDL reduces atherosclerosis in hyperlipidemic animals. The nature of athero-protective antigenic epitopes in LDL remains unclear. We have recently identified nearly a 100 antigenic epitopes in human apo B-100 and in this study we evaluated the effects of immunization with two such epitopes on atherosclerosis in hypercholesterolemic apo E (-/-) mice. Male apo E (-/-) mice were immunized at 6-7 weeks of age with two different apo B-100 related peptide sequences using alum as adjuvant and mice immunized with alum alone served as controls. Peptide-2 immunization reduced aortic atherosclerosis by 40% and plaque inflammation by 80% compared to controls without a reduction in circulating cholesterol levels whereas Peptide-1 immunization had no effect. Peptide-2 immunization also reduced the progression of aortic lesions when mice were immunized at 16 weeks of age, suggesting the possibility of immuno-modulation in treating established atherosclerosis. The athero-protective effect of Peptide-2 immunization was absent in splenectomized mice but could be conveyed to non-immunized mice via adoptive transfer of splenocytes from peptide-2 immunized mice. In conclusion, immunization with a specific apo B-100 related peptide sequence reduces aortic atherosclerosis and plaque inflammation. Such acquired immunity and athero-protective effect appears to be mediated by splenocytes. These data demonstrate the feasibility of peptide based immunomodulating therapy for atherosclerosis.
Chyu
Kuang-Yuh
KY
Atherosclerosis Research Center, Division of Cardiology, Department of Medicine and Burns and Allen Research Institute, Cedars-Sinai Medical Center and David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Zhao
Xiaoning
X
Reyes
Odette S
OS
Babbidge
Stephanie M
SM
Dimayuga
Paul C
PC
Yano
Juliana
J
Cercek
Bojan
B
Fredrikson
Gunilla Nordin
GN
Nilsson
Jan
J
Shah
Prediman K
PK
D019264:Adoptive Transfer; D000818:Animals; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000276:immunology*; D001057:Apolipoproteins E / Q000172:deficiency*; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control* / Q000628:therapy; D002784:Cholesterol / Q000097:blood; D000939:Epitopes / Q000276:immunology*; D006937:Hypercholesterolemia / Q000276:immunology* / Q000473:pathology; D007114:Immunization; D016219:Immunotherapy, Adoptive; D007249:Inflammation / Q000628:therapy; D008297:Male; D051379:Mice; D013154:Spleen / Q000166:cytology
D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D000939:Epitopes; D002784:Cholesterol