Abstract
Proapoptotic Bcl-2 family member Bim is particularly relevant for deletion of autoreactive and activated T and B cells, implicating Bim in autoimmunity. As atherosclerosis is a chronic inflammatory process with features of autoimmune disease, we investigated the impact of hematopoietic Bim deficiency on plaque formation and parameters of plaque stability. Bim(-/-) or wild type bone marrow transplanted ldlr(-/-) mice were fed a Western type diet (WTD) for 5 or 10 weeks, after which they were immunophenotyped and atherosclerotic lesions were analyzed. Bim(-/-) transplanted mice displayed splenomegaly and overt lymphocytosis. CD4(+) and CD8(+) T cells were more activated (increased CD69 and CD71 expression, increased interferon gamma production). B cells were elevated by 147%, with a shift towards the pro-atherogenic IgG-producing B2 cell phenotype, resulting in a doubling of anti-oxLDL IgG1 antibody titers in serum of bim(-/-) mice. Bim(-/-) mice displayed massive intraplaque accumulation of Ig complexes and of lesional T cells, although this did not translate in changes in plaque size or stability features (apoptotic cell and macrophage content). The surprising lack in plaque phenotype despite the profound pro-atherogenic immune effects may be attributable to the sharp reduction of serum cholesterol levels in WTD fed bim(-/-) mice.
Original language | English |
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Article number | 3086 |
Number of pages | 11 |
Journal | Scientific Reports |
Volume | 7 |
DOIs | |
Publication status | Published - 8 Jun 2017 |
Keywords
- LOW-DENSITY-LIPOPROTEIN
- FAMILY-MEMBER BIM
- HUMAN ATHEROSCLEROTIC PLAQUES
- T-CELL DEATH
- BCL-2 FAMILY
- OXIDIZED LDL
- B-CELLS
- DENDRITIC CELLS
- TRANSGENIC MICE
- IMMUNITY