A novel Nanocellulose-Gelatin-AS-IV external stent resists EndMT by activating autophagy to prevent restenosis of grafts

Abstract

Vein grafts are widely used for coronary artery bypass grafting and hemodialysis access, but restenosis remains the "Achilles' heel" of these treatments. An extravascular stent is one wrapped around the vein graft and provides mechanical strength; it can buffer high arterial pressure and secondary vascular dilation of the vein to prevent restenosis. In this study, we developed a novel Nanocellulose-gelatin hydrogel, loaded with the drug Astragaloside IV (AS-IV) as an extravascular scaffold to investigate its ability to reduce restenosis. We found that the excellent physical and chemical properties of the drug AS-IV loaded Nanocellulose-gelatin hydrogel external stent limit graft vein expansion and make the stent biocompatible. We also found it can prevent restenosis by resisting endothelial-to-mesenchymal transition (EndMT) in vitro. It does so by activating autophagy, and AS-IV can enhance this effect both in vivo and in vitro. This study has added to existing research on the mechanism of extravascular stents in preventing restenosis of grafted veins. Furthermore, we have developed a novel extravascular stent for the prevention and treatment of restenosis. This will help optimize the clinical treatment plan of external stents and improve the prognosis in patients with vein grafts.

Graphical abstract

Schematic of the Nanocellulose-Gelatin-AS-IV extravascular stent in the inhibition of endothelial-to-mesenchymal transition through the autophagy pathway.

Highlights

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  The NC-Gelatin extravascular stent has suitable physicochemical properties to prevent restenosis of the grafted veins.

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  The NC-Gelatin extravascular stent has excellent biocompatibility, which is critical for grafting veins.

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  The NC-Gelatin extravascular stent prevents restenosis by activating autophagy against EndMT.

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  AS-IV can enhance the effect of the stent to activate autophagy against EndMT.