Immunization with cationized BSA inhibits progression of disease in ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis.
Immune responses against modified self-antigens generated by hypercholesterolemia play an important role in atherosclerosis identifying the immune system as a possible novel target for prevention and treatment of cardiovascular disease. It has recently been shown that these immune responses can be modulated by subcutaneous injection of adjuvant. In the present study we immunized 25-week old ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis with adjuvant and two different concentrations of the carrier molecule cationized BSA (cBSA). Plasma levels of Th2-induced apolipoprotein B (apoB)/IgG1 immune complexes were increased in the cBSA immunized groups verifying induction of immunity against a self-antigen. Mice were sacrificed at 36 weeks of age and atherosclerosis was monitored by en face Oil red O staining of the aorta. Immunization with 100 μg cBSA inhibited plaque progression, whereas the lower dose (50 μg) did not. In addition, the higher dose induced a more stable plaque phenotype, indicated by a higher content of collagen and less macrophages and T cells in the plaques. Moreover, there was an increased ratio of Foxp3+/Foxp3⁻ T cells in the circulation suggesting activation of a regulatory T cell response. In conclusion, we show that immunization with cBSA induces an immune response against apoB as well as an activation of Treg cells. This was associated with development of a more stable plaque phenotype and reduced atherosclerosis progression.
Department of Clinical Sciences, Skane University Hospital in Malmö, Lund University, Sweden.
Daniel
D
Kolbus
Maria
M
Wigren
Irena
I
Ljungcrantz
Ingrid
I
Söderberg
Ragnar
R
Alm
Harry
H
Björkbacka
Jan
J
Nilsson
Gunilla N
GN
Fredrikson
D000071479:APOBEC-1 Deaminase; D000818:Animals; D000936:Antigen-Antibody Complex / Q000097:blood; D001021:Aortic Valve / Q000276:immunology / Q000473:pathology; D001055:Apolipoproteins B / Q000097:blood / Q000276:immunology; D050197:Atherosclerosis / Q000276:immunology* / Q000503:physiopathology*; D001835:Body Weight / Q000276:immunology; D017252:CD3 Complex / Q000276:immunology; D002784:Cholesterol / Q000097:blood; D003564:Cytidine Deaminase / Q000172:deficiency*; D016207:Cytokines / Q000276:immunology; D018450:Disease Progression; D005260:Female; D007114:Immunization; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D011973:Receptors, LDL / Q000172:deficiency* / Q000378:metabolism; D012710:Serum Albumin, Bovine / Q000737:chemistry / Q000276:immunology*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology
D000936:Antigen-Antibody Complex; D001055:Apolipoproteins B; D017252:CD3 Complex; D016207:Cytokines; D007074:Immunoglobulin G; D011973:Receptors, LDL; D012710:Serum Albumin, Bovine; D002784:Cholesterol; D000071479:APOBEC-1 Deaminase; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase