Reduced transplant arteriosclerosis in murine cardiac allografts placed in interferon-gamma knockout recipients. |
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Authors: | A. R is nen-Sokolowski, T. Glysing-Jensen, J. Koglin, M. E. Russell |
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Affiliation: | A. Räisänen-Sokolowski, T. Glysing-Jensen, J. Koglin, and M. E. Russell |
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Abstract: | To investigate the functional role of interferon (IFN)-gamma in transplant arteriosclerosis, BALB/c hearts were transplanted in immunosuppressed C57BL/6J recipients with (n = 10) or without (n = 10) targeted IFN-gamma gene deletion. In 55-day heart allografts, IFN-gamma deficiency resulted in a significant decrease in vascular thickening. The severity of intimal thickening measured as the percentage of luminal occlusion (mean +/- SEM) in all elastin stained vessels (n = 410) decreased from 37+/-5% in wild-type recipients to 18+/-5% in IFN-gamma -/- recipients (P < 0.005). In the few diseased vessels in grafts from IFN-gamma -/- recipients, the neointima was more cellular with a 90% increase in the nuclear density. This finding correlated with a 50% reduction in fibrosis estimated by alpha-smooth muscle actin cell accumulation in the neointima. The reduction in severity and altered composition of vascular thickening in grafts from IFN-gamma -/- recipients shows that IFN-gamma contributes to arteriosclerotic development following transplantation. |
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