[Effects of FOXP3 on the progression of atherosclerosis plaque in ApoE-knock out mice]

Abstract

Aim: To explore effects of FOXP3 on the progression of atherosclerosis plaque in hypercholesterolemic apoliprotein(apo)E-/- mice.

Methods: At 8 weeks of age, 32 male ApoE-/- mice were randomly divided into four groups of eight. Labeled: negative control group, positive control group, small interfering RNA (siRNA) group, and regulatory T cells transfer (Tregs) group. Lentivirus-mediated (siRNA) identified its function by Western blot was used to knock down FOXP3 and Foxp3(high+);CD4(+); CD25(+); Tregs acquired through magnetic activated cell sorting adoptive transfer assays in high fat diet ApoE-/- mice were done. The resulting atherosclerotic lesions were assessed by determining the number and function of CD4(+);CD25(+); Tregs, FOXP3 transcript levels and investigating the expression of Foxp3 protein in different tissues. Inflammatory cytokines were determined by ELISA.

Results: Animals treated with siRNA of FOXP3 showed a significant increase in atherosclerotic lesion formation and a reduction in the number and function of Foxp3(+);CD4(+);CD25(+); Tregs compared with other groups. Transfer of Foxp3(high+);CD4(+);CD25(+); Tregs significantly decreased atherosclerotic plaque formation and increased the number and function of Foxp3(+); CD4(+); CD25(+); Tregs. Foxp3 protein levels and FOXP3 transcript levels were lowest in the siRNA group, and were highest in tissues from the Tregs transfer group.

Conclusion: FOXP3 plays an important role in regulating the inflammatory response within the atherosclerotic lesion. It can inhibit significant the progression of the atherosclerosis plaque in ApoE-/- mice.