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Transplantation-Induced Functional/Morphological Changes in Rat Aorta Allografts Differ from Those in Arteries of Rat Kidney Allografts
Authors:Emile Andriambeloson  Catherine Cannet  Charles Pally  Bernd Klanke  Christian Bruns  Hans-Günter Zerwes and  Marc Bigaud
Institution:Novartis Pharma AG, Transplantation Research Global Business Unit, Basel, Switzerland.
Abstract:The functional/morphological changes observed in rat aorta allografts were compared with those seen in the arteries of rat kidney allografts. Untreated allografts (F344-to-LEW) were collected at various times post-transplantation (Tx). Vascular smooth muscle cell (SMC) constriction to phenylephrine (Phe) and endothelial cell (EC)-dependent relaxation to acetylcholine (Ach) were assessed. Neointima formation in graft vessels was assessed by histology. In aorta allografts, the effects of Phe and Ach were irreversibly abolished within 3-2 weeks post-Tx. Neointima formation was consistently detected between 4 and 8 weeks post-Tx. In kidney allografts, sign of vasculopathy was seen in 10, 30 and 40% of resistance arteries at 8, 16 and 33 weeks post-Tx, respectively. In the main renal artery, substantial neointima formation was not apparent before 33 weeks post-Tx, the vasoconstrictor effect of Phe was fully maintained until then, and Ach-induced vasorelaxation was irreversibly reduced by approximately 70% from week 2 post-Tx onwards. These results indicate that the post-Tx functional/morphological changes seen in aorta allografts do not reflect those seen in arteries of kidney allografts. Hence, renal arteries from rat kidney allografts can be considered as a more relevant model to study the cascade of events leading to Tx-induced CGA in solid organ allografts.
Keywords:Aorta allograft  chronic graft arteriosclerosis  kidney allograft  rat  vascular function
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