Cardiovascular Research Advance Access originally published online on September 13, 2008
Cardiovascular Research 2008 80(2):175-180; doi:10.1093/cvr/cvn250
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Deficiency of tumour necrosis factor-
and interferon-
in bone marrow cells synergistically inhibits neointimal formation following vascular injury
1 Department of Cardiovascular Medicine, Shinshu University Graduate School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621, Japan
2 Department of Infection and Host Defense, Shinshu University Graduate School of Medicine, Matsumoto, Japan
3 Frontier Research Center, Tokyo Institute of Technology, Yokohama, Japan
4 Basic Research Programs PRESTO, Japan Science and Technology Agency, Kawaguchi, Japan
5 Institutee of Medical Science, University of Tokyo, Tokyo, Japan
* Corresponding author. Tel: +81 263 37 3352; fax: +81 263 37 2573. E-mail address: masafumi{at}shinshu-u.ac.jp
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-
(TNF-) and interferon-
(IFN-) in the neointimal formation after injury.
Methods and results: Control (BALB/c), TNF--deficient (Tnf–/–), IFN--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- and IFN- 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- and IFN- specifically in bone marrow cells significantly inhibited neointimal formation after vascular injury.
Conclusion: The absence of TNF- and IFN- 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
Time for primary review: 11 days