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• W1970599993 abstract "Ischemia-induced tissue activation may contribute to the pathogenesis of graft vasculopathy, but the mediators implicated have only partially been characterized. To gain further insight into the molecular mechanisms involved, syngeneic rat aortic transplants with cold-storage-induced vasculopathy were studied for differentially expressed mRNA transcripts. Vessel segments were exposed to either 1 or 18 hours of cold ischemia, followed by transplantation into syngeneic recipients. After 3 days or 4 weeks, the grafts were removed and total mRNA was isolated and used for differential display to identify modulation of transcript expression related to prolonged storage. Using 15 sets of random primers, 17 polymerase chain reaction products were up-regulated and 2 were downregulated in grafts exposed to 18 hours of ischemia. Sequencing of these amplicons showed that 6 had a high degree of homology to known sequences whereas 13 had no homology to any of the genes in the database. Two of the differentially displayed amplicons (capping protein and eotaxin) were cloned, re-amplified, and used as probes for Northern blot analysis to confirm their differential expression. Immunohistochemistry using monoclonal antibodies against capping protein-alpha and eotaxin confirmed that both proteins are expressed in the media of normal aortas and that there was an increased expression in vessels exposed to prolonged ischemia albeit that the increase at the protein level seemed less compared with changes in transcript expression. Northern blots with RNA from aortic allografts exposed to prolonged ischemic storage also showed increased levels of capping protein and eotaxin mRNA whereas there was a decrease in the relative amount of these transcripts in vessels exposed to balloon denudation, suggesting that the increase after prolonged ischemic exposure is not the result of a nonspecific response to injury. Based on the biological characteristics of capping protein and eotaxin it is conceivable that they play a pathogenetic role in ischemia-induced vessel wall remodeling. It remains to be established whether these genes or their products serve as target molecules for therapeutic interventions to prevent or treat cold-storage-induced graft vasculopathy." @default.
• W1970599993 created "2016-06-24" @default.
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• W1970599993 date "1998-07-01" @default.
• W1970599993 modified "2023-10-14" @default.
• W1970599993 title "Eotaxin and Capping Protein in Experimental Vasculopathy" @default.
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• W1970599993 doi "https://doi.org/10.1016/s0002-9440(10)65548-4" @default.
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