Abstract | AIMS: 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)
|