[Show abstract][Hide abstract] ABSTRACT: Interferon (IFN)-γ has been implicated in restenosis, however its precise role in the pathophysiology of neointimal formation following angioplasty is unclear, as it has been shown to both promote and inhibit neointimal formation. Dietary-induced hypercholesterolemia enhances injury-mediated neointimal formation, associated with increased systemic inflammation and serum IFN-γ. This study examined the effect of IFN-γ gene deficiency ((-/-)) on neointimal formation in a mouse model of endothelial injury combined with an atherogenic diet. Neointimal formation was induced via endoluminal endothelial injury of the common iliac arteries of IFN-γ(-/-) and wild-type (WT) C57Bl/6 mice. Histopathological analysis of the arteries was performed at 3 and 6 weeks post-surgery. IFN-γ(-/-) mice demonstrated a significant reduction in neointimal formation at the 3-week time point, compared to their WT counterpart. No significant differences in plasma lipid profile and the extent of re-endothelialization were detected between IFN-γ(-/-) and WT mice, suggesting that the effect of IFN-γ on neointimal formation is due to injury-mediated vessel neointimal responses. In support of the histopathological findings, immunohistochemical analysis revealed a significant reduction in vessel infiltrating macrophages, and neointimal PDGF-B expression, vascular smooth muscle cell composition and cellular proliferation in the IFN-γ(-/-) mice, in comparison to their corresponding WT group at the 3-week time point. In conclusion, the IFN-γ-mediated pathway plays an important role in inflammatory responses and proliferative effects following injury, suggesting that modulation of the IFN-γ pathway would be beneficial in controlling neointimal formation and restenosis.
Full-text · Article · Jun 2012 · International Journal of Molecular Medicine
[Show abstract][Hide abstract] ABSTRACT: CD4+CD25+ regulatory T (Treg) cells play a crucial role in maintaining self-tolerance and preventing autoimmune disease. The transcription factor forkhead box protein 3 (Foxp3) has been identified as a molecular marker for Treg cells. Foxp3 is highly expressed in lymphoid tissue and several signalling pathways influence its expression. It plays an essential role in the development and function of Treg cells. Mutations in Foxp3 are responsible for the scurfy (sf) mutant mouse, and for autoimmune human diseases including the X-linked fatal "immune dysregulation, polyendocrinopathy, enteropathy, X-linked" (IPEX), autoimmune colitis and rheumatoid arthritis. Recent studies have also revealed an important and novel anti-atherogenic role for Treg cells and consequently for Foxp3. These data open up potential novel therapeutic avenues for the management of atherosclerosis.
Full-text · Article · Nov 2007 · The International Journal of Biochemistry & Cell Biology