Background: Inflammatory stimuli induced by
NF-kB drive atherosclerotic lesion formation. The epigenetic P300/CBP associated factor (PCAF) post-transcriptionally acetylates FoxP3, which is required for regulatory T-cell (Treg) differentiation and immune modulation. We hypothesize that PCAF deficiency affects
atherosclerosis via regulation of regulatory Tregs. Method:
ApoE3*Leiden (n = 13) and
ApoE3*LeidenxPCAF-/- (n = 13) were fed a high-fat diet (HFD) containing 1.25%
cholesterol. Systemic FoxP3+ T cells were measured every 4 weeks by flow cytometry (n = 6). After 5-months of HFD, mice were euthanized, and hearts and blood were collected.
IL-6 and TNFα concentrations were measured in plasma to identify systemic inflammatory responses. Compositional and morphometrical analyses were performed on the atherosclerotic lesions in the aortic sinuses. Results: After 5 months of HFD, plasma
cholesterol concentrations were not different for
ApoE3*LeidenxPCAF-/- compared to
ApoE3*Leiden mice. Expression of FoxP3 by systemic CD4+ T cells decreased 1.8 fold in
ApoE3*LeidenxPCAF-/- after 5 months HFD and remained significantly reduced after 5 months of HFD. Systemic TNFα and
IL-6 concentrations were comparable, whereas the atherosclerotic lesion size in
ApoE3*LeidenxPCAF-/- mice was increased by 28% compared to
ApoE3*Leiden mice. In atherosclerotic lesions, no differences were observed in macrophage differentiation or VSMC content, although a small increase in
collagen was identified. Conclusion: Our data show that PCAF deficiency resulted in a decrease in circulatory FoxP3+ regulatory T cells and ameliorated atherosclerotic lesions with no differences in systemic
inflammation or macrophage differentiation in the atherosclerotic lesions. This suggests that PCAF regulates
atherosclerosis via modulation of FoxP3+ regulatory T cell differentiation.