Leukocyte Bim deficiency does not impact atherogenesis in ldlr(-/-) mice, despite a pronounced induction of autoimmune inflammation

Lieve Temmerman*, Marijke M. Westra, Ilze Bot, Bart J. M. van Vlijmen, Niek Van Bree, Martine Bot, Kim L. L. Habets, Tom G. H. Keulers, Johan van der Vlag, Thomas G. Cotter, Theo J. C. van Berkel, Erik A. L. Biessen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Web of Science)

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 languageEnglish
Article number3086
Number of pages11
JournalScientific Reports
Volume7
DOIs
Publication statusPublished - 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

Cite this