2001 Fiscal Year Final Research Report Summary
An experimental study developing new therapeutic strategy for cardiac allograft vasculopathy : selective chemokine/receptor systems as molecular targets
| Project/Area Number |
12557113
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 展開研究 |
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| Research Field |
Thoracic surgery
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| Research Institution | Osaka University |
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Principal Investigator |
SAKAKIDA Satoru Osaka University, Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (90311753)
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| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIMA Norihide Osaka University, Graduate School of Medicine, Assistant, 医学系研究科, 助手 (30263247)
SAWA Yoshiki Osaka University, Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00243220)
SHIRAKURA Ryota Osaka University, Graduate School of Medicine, Professor, 医学系研究科, 教授 (00116047)
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| Project Period (FY) |
2000 – 2001
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| Keywords | Chronic rejection / heterotopic rat heart transplantation / Retransplantation / quantitative RT-PCR / aortic transplantation / Chemokine / CXCR3 |
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| Research Abstract |
Chemokine systems are likely to play a role in transplant vasculopathy ; however, a comprehensive study of the expression of chemokines and their receptors in this disease has not been performed. The expression of all the rat chemokines and chemokine receptor genes for which the nucleotide sequences are known were quantitatively monitored by the fluorescence-based real time RT-PCR technique, and selected cytokine-receptor pairs were determined by immunohistochemical staining. The analysis covered the whole time course of transplant vasculopathy in two different graft models (cardiac and aortic grafts) with five different strain combinations of rats. Among the 13 receptor genes examined, the CXCR3, CCR5, and CCR2 genes and those of their corresponding ligands were selectively and strongly induced in grafts developing transplant vasculopathy. The expression patterns of the receptors were similar in both cardiac and aortic allografts, although their induction as well as their absolute levels of expression were amplified several fold in the grafted aorta compared with heart grafts. The genes were already induced before morphological changes became apparent and their expression was sustained over the whole period of neointimal formation. Interestingly, immunohistochemical staining for IP10 and CXCR3 showed unique patterns of expression : We found IP10 expression around the diseased vessels and CXCR3 expression in the innermost layer of the neointima. This study suggested diagnostic as well as potential functional roles of the chemokine/receptor pairs, IP10-CXCR3, RANTES-CCR5, and MCP1-CCR2, in rat models of transplant vasculopathy. In addition, the three chemokine/receptor systems were identified as the reasonable therapeutic targets for the disease.
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