Complete loss of functional smooth muscle cells precedes vascular remodeling in rat aorta allografts

Background. The functional consequences of vascular remodeling in rat aorta allografts were studied at different times after transplantation (Tx). Methods. At days 1, 3, 7, 14, 28, and 56 after Tx, rat aorta allografts (Da rk Agouti [DA]-to-Lewis) were mounted as isolated organs, and their contrac tile properties tested with phenylephrine, KCl, or endothelin-1, Controls w ere native DA-aortae and DA-syngeneic grafts. Changes in alpha smooth muscl e actin and morphology were assessed by immunoblotting and histology. Results. PostTx syngeneic grafts presented similar functional and morpholog ical properties to native aortae. In allografts, no morphological changes w as detected at day 7 after Tx, but phenylephrine-induced vasoconstriction w as reduced by 60%, Signs of medial smooth muscle cell (SMC) loss and advent itial inflammation were observed at day 14 after Tx, without neointima form ation. A complete loss of contractile property was observed at day 28 after Tx in association with a 75% decrease in alpha-SMC actin, severe adventiti al inflammation, and reduced medial cellularity. At this time, neointima wa s restricted to both edges of allografts. At day 56 after Tx, allografts we re also not functional and exhibited neointima on their entire length. All these changes were prevented by treating recipients with cyclosporine (7.5 mg/kg/day). Conclusion. These results indicate that, after Tx, the contractile property of rat aorta allografts is altered before manifest vascular remodeling. Be cause this can be prevented by cyclosporine, it most likely reflects an acu te rejection of SMC. These results also show that vascular graft dysfunctio n can be used to monitor the development of rejection in the rat aorta allo graft model.