Extravascular rapamycin film inhibits the endothelial-to-mesenchymal transition through the autophagy pathway to prevent vein graft restenosis.

Abstract

Following vein grafting, the vein must adapt to arterial hemodynamics, which can lead to intimal hyperplasia (IH) and restenosis. Moreover, endothelial-to-mesenchymal transition (EndMT) components are highly associated with IH. Therefore, in this study, we aimed to design an extravascular film loaded with rapamycin (extravascular rapamycin film [ERF]) to limit vein graft stenosis. The film exhibited stable physicochemical properties as well as in vivo and in vitro biocompatibility. In vivo, the film inhibited the EndMT by activating the autophagy pathway. Moreover, rapamycin enhanced this biological effect. Collectively, these findings highlighted the applicability of ERF as a new therapeutic target for preventing vein graft restenosis.