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- W2893505328 abstract "Background Transplant vasculopathy is a major cause of chronic rejection of transplanted organs. In the present study, we examined the effects of CX-5461, a novel selective inhibitor of RNA polymerase I, on development of transplant vasculopathy using a modified model of rat aortic transplantation. Methods The thoracic aortas from Fischer rats were transplanted into the abdominal cavity of Lewis rats. CX-5461 was mixed in pluronic gel and administered via perivascular release. Results Treatment with CX-5461 mitigated the development of neointimal hyperplasia and vascular inflammation. This effect was likely to be attributable in part to inhibition of macrophage-dependent innate immunity reactions. Specifically, CX-5461 exhibited potent inhibitory effects on macrophage migration and lipopolysaccharide-induced activation. Treatment with CX-5461 also prevented macrophage differentiation and maturation from primary bone marrow cells. In macrophages, CX-5461 did not alter the total amount of p53 protein, but significantly increased p53 phosphorylation, which was involved in regulating cytokine-stimulated macrophage proliferation. Conclusions In conclusion, our results suggest that pharmacological inhibition of RNA polymerase I may be a novel strategy to treat transplantation-induced arterial remodeling." @default.
- W2893505328 created "2018-10-05" @default.
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- W2893505328 date "2018-10-01" @default.
- W2893505328 modified "2023-10-04" @default.
- W2893505328 title "The Selective RNA Polymerase I Inhibitor CX-5461 Mitigates Neointimal Remodeling in a Modified Model of Rat Aortic Transplantation" @default.
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- W2893505328 doi "https://doi.org/10.1097/tp.0000000000002372" @default.
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