Zedoary Guaiane-Type Sesquiterpenes-Eluting Stents Accelerate Endothelial Healing Without Neointimal Hyperplasia in a Porcine Coronary Artery Model

Abstract

Objective: The effects of zedoary guaiane-type sesquiterpenes (ZGS)-based eluting stent (ZES) in accelerating reendothelialization and inhibiting neointimal hyperplasia were examined in a porcine coronary artery model. Methods: The ZES was prepared by polymer-free 316L stainless metal stents. Sirolimus-eluting stents (SES) and bare metal stents (BMS) with identical platforms were used as controls. Stents with 15 mm in length and 2.0 to 3.5 mm in diameter were implanted in porcine coronary arteries. Scanning electron microscopy (SEM) and histopathology were performed to assess the reendothelialization and neointimal hyperplasia. The 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyl-2H-tetrazoliumbromide assay and flow cytometry were used to assess the influence of ZGS on human umbilical vascular endothelial cells (HUVECs). Results: At 7 days, SEM showed that percentage of endothelial coverage area was 94.04% ± 5.01% for ZES, 47.59% ± 19.91% for SES ( P < .01 for ZES vs SES), and 59.58% ± 19.61% for BMS ( P < .05 for ZES vs BMS). At 28 days, the percentage of coverage area was 98.51% ± 1.86% for ZES, 86.18% ± 8.16% for SES ( P < .05 for ZES vs SES), and 94.26% ± 5.58% for BMS. Neointimal area and stenosis were significantly lower in ZES (1.07 ± 0.48 mm2, 27.66% ± 12.20%) compared to BMS (1.73 ± 0.69 mm2, 44.08% ± 15.03%, both P < .01, respectively), with no difference in SES (0.94 ± 0.12 mm2, 28.87% ± 6.00%, both P > .05, respectively). The ZGS also promoted HUVECs viability and improved HUVECs proliferation compared to sirolimus. Conclusion: The ZES accelerated reendothelialization and suppressed neointimal hyperplasia in a porcine coronary artery model, with beneficial effects on HUVECs.