42| Volume 213, ISSUE 1, e18, November 2010

Increased foam cell formation and atherosclerotic plaque apoptosis in LDLr−/− mice lacking macrophage Mcl-1

      The anti-apoptotic Bcl-1 family member Mcl-1 plays an important, in neutrophils essential, role in leukocyte survival and differentiation. Here, we investigated the impact of Mcl-1 deletion in myeloid cells on atherosclerosis in WTD fed LDLr−/−. First, Mcl-1−/− peritoneal macrophages had an increased sensitivity to Ox-LDL induced cell death and showed altered expression of several pro-apoptotic Bcl-2 family members as compared to WT macrophages. In keeping apoptotic cell content in aortic root lesions of Mcl-1−/− chimeras was elevated by 77% compared to WT controls. Second lipid uptake by peritoneal Mcl-1−/− macrophages was enhanced in vitro as well as in vivo. Third, Mcl-1−/− macrophages showed a clear shift towards a pro-inflammatory M1 phenotype as apparent from their cytokine expression pattern and reduced phagocytotic capacity. Despite these profound pro-atherogenic effects of Mcl-1 deficiency both plaque development and progression did not differ between Mcl-1−/− and WT BM recipients. This seeming paradox may well be imputed to altered neutrophil numbers and migratory capacity in Mcl-1 deficiency, attenuating lesional neutrophil infiltration.
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