Journal Article

Deficiency of tumour necrosis factor-α and interferon-γ in bone marrow cells synergistically inhibits neointimal formation following vascular injury

Hideki Murayama, Masafumi Takahashi, Masaya Takamoto, Yuji Shiba, Hirohiko Ise, Jun Koyama, Yoh-ichi Tagawa, Yoichiro Iwakura and Uichi Ikeda

in Cardiovascular Research

Published on behalf of European Society of Cardiology

Volume 80, issue 2, pages 175-180
Published in print November 2008 | ISSN: 0008-6363
Published online September 2008 | e-ISSN: 1755-3245 | DOI: https://dx.doi.org/10.1093/cvr/cvn250
Deficiency of tumour necrosis factor-α and interferon-γ in bone marrow cells synergistically inhibits neointimal formation following vascular injury

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Aims

Neointimal formation after percutaneous coronary intervention (PCI), termed restenosis, limits therapeutic revascularization. Since it is now known that vascular injury involves an inflammatory response, we examined the role of tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the neointimal formation after injury.

Methods and results

Control (BALB/c), TNF-α-deficient (Tnf−/−), IFN-γ-deficient (Ifng−/−), or double-deficient (Tnf−/−Ifng−/−) mice were subjected to wire-mediated vascular injury of the right femoral artery. Neointimal formation after injury was significantly reduced after the injury in the Tnf−/−Ifng−/− mice, compared to that in the control, Tnf−/−, and Ifng−/− mice. Immunohistochemical analysis showed that TNF-α and IFN-γ were expressed in neointimal lesions in the control mice, but not in mice with deficiency of the corresponding cytokine. No significant difference in re-endothelialization was observed among these groups. The number of proliferating cell nuclear antigen in the neointimal lesions was significantly decreased in the Tnf−/−Ifng−/− mice. Bone marrow transplantation experiments revealed that deficiency of TNF-α and IFN-γ specifically in bone marrow cells significantly inhibited neointimal formation after vascular injury.

Conclusion

The absence of TNF-α and IFN-γ in bone marrow cells synergistically inhibits neointimal formation following vascular injury, and thus, may provide new insights into the mechanisms underlying restenosis after PCI.

Keywords: Bone marrow cell; Cytokine; Inflammation; Restenosis

Journal Article.  3122 words.  Illustrated.

Subjects: Cardiovascular Medicine

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