Pioglitazone modulates the balance of effector and regulatory T cells in apolipoprotein E deficient mice

Background and aims: Pioglitazone (PIO) affects T cell-mediated immunity through actions of peroxisome proliferator activated receptor γ (PPARγ). Effector and regulatory T cells control the development of atherosclerosis, a chronic inflammatory disease affecting the arterial blood vessels. The aim of this study was to examine whether PIO ameliorates atherosclerosis by altering the balance of effector and regulatory T cells. Methods and results: To explore the effect of PIO on early and advanced atherosclerosis, apolipoprotein E deficient (ApoE-/-) mice were fed western diet and received PIO (20mg/kg/day) by gastric gavage at 6 or 14 weeks of age, respectively for 8 weeks. Data showed PIO markedly inhibited early fatty streak formation. Further, although the advanced fibrofatty plaque sizes were not significantly reduced, the numbers of smooth muscle cells within lesions were increased and higher collagen concentrations were produced. In general, macrophage expression in lesions was decreased. Additionally, the expression of Foxp3⁺ cells was increased in lesions and spleens in mice at all PIO treatment stages, whereas the CD4⁺IFN-γ⁺/CD4⁺IL-4⁺ cell ratios were reduced. Conclusion: PIO inhibited early atherosclerotic lesion formation and increased the stability of advanced atherosclerotic plaques in ApoE-/- mice, which was associated with altering the balance of effector and regulatory T cells.