Propylthiouracil-coated biodegradable polymer inhibited neointimal formation and enhanced re-endothelialization after vascular injury

Shang Hung Chang, Cheng Hung Lee, Yung Hsin Yeh, Shih Jung Liu, Chao Jan Wang, Ming Yi Hsu, Wei Jan Chen*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

3 Scopus citations

Abstract

Background: The drug-eluting stent is a standard approach for the treatment of coronary artery disease. Propylthiouracil (PTU), an antithyroid drug, has been proven to suppress neointimal formation after balloon injury. Materials and methods: This study used a biodegradable polymer coating with PTU to test its effects on platelet function, re-endothelialization, and neointimal formation after vascular injury. Electrospinning was used to fabricate hybrid stents and generate PTU-loaded nanofibers. Results: PTU-eluting stents maintained a stable release of PTU for 3 weeks. The PTU-coated stent markedly decreased the neointimal formation induced by vascular injury in the descending aorta of rabbits. Moreover, the PTU coating reduced platelet adhesion on the surface of the biodegradable membrane, which was reflected by the decreased expression of adhesion molecule in PTU-treated endothelial cells. The PTU coating enhanced re-endothelialization in injured aortas. In vitro, PTU exerted less suppressive effect on the proliferation and migration of endothelial cells than on those of vascular smooth muscle cells. Furthermore, treatment of endothelial cells with PTU induced phosphorylation (Ser1177) of endothelial nitric oxide synthase as well as its association with heat shock protein 90, supporting the protective role of PTU in endothelial function. The level of thyroid-stimulating hormone remained unchanged during the experimental period. Conclusion: This study indicates that PTU can be released locally and steadily in injured aortas, with some local effects but without systemic effects. Furthermore, PTU-coated stents may have beneficial effects on neointimal formation, endothelial cell, and platelet functions.

Original languageEnglish
Pages (from-to)1761-1771
Number of pages11
JournalInternational Journal of Nanomedicine
Volume13
DOIs
StatePublished - 21 03 2018

Bibliographical note

Publisher Copyright:
© 2018 Chang et al.

Keywords

  • Drug-eluting stent
  • Endothelial cell
  • Neointimal formation
  • Platelet
  • Propylthiouracil

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