Deficiency of tumour necrosis factor-alpha and interferon-gamma in bone marrow cells synergistically inhibits neointimal formation following vascular injury.

Abstract

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-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in the neointimal formation after injury.

METHODS AND RESULTS:

Control (BALB/c), TNF-alpha-deficient (Tnf(-/-)), IFN-gamma-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-alpha and IFN-gamma 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-alpha and IFN-gamma specifically in bone marrow cells significantly inhibited neointimal formation after vascular injury.

CONCLUSION:

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

• Authors: Hideki Murayama, Masafumi Takahashi, Masaya Takamoto, Yuji Shiba, Hirohiko Ise, Jun Koyama, Yoh-Ichi Tagawa, Yoichiro Iwakura, Uichi Ikeda
• Journal: Cardiovascular research (Cardiovasc Res) Vol. 80 Issue 2 Pg. 175-80 (Nov 01 2008) ISSN: 0008-6363 [Print] England
• PMID: 18791204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Tumor Necrosis Factor-alpha
• Interferon-gamma

Topics

• Animals
• Arterial Occlusive Diseases (immunology, pathology, prevention & control)
• Bone Marrow Cells (immunology)
• Bone Marrow Transplantation
• Cell Proliferation
• Constriction, Pathologic
• Disease Models, Animal
• Endothelial Cells (pathology)
• Femoral Artery (immunology, injuries, pathology)
• Interferon-gamma (deficiency, genetics)
• Macrophages (pathology)
• Male
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Myocytes, Smooth Muscle (pathology)
• Tumor Necrosis Factor-alpha (deficiency, genetics)
• Tunica Intima (immunology, injuries, pathology)