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Interferon-γ deficiency reduces neointimal formation in a model of endoluminal endothelial injury combined with atherogenic diet

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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 3week 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 IFNγmediated 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.
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Document Type: Research Article

Affiliations: 1: Discipline of Pathology, School of Medical Sciences and Bosch Institute, The University of Sydney, Sydney, New South Wales, Australia 2: Department of Clinical Biochemistry, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia

Publication date: January 1, 2012

More about this publication?
  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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