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- Title
A novel PDGF receptor inhibitor-eluting stent attenuates in-stent neointima formation in a rabbit carotid model.
- Authors
CHEN HUANG; HAIJUN MEI; MIN ZHOU; XIAOBING ZHENG
- Abstract
A novel drug-eluting stent (DES) is required to target vascular smooth muscle cells (SMCs) without harming endothelial cells (ECs). Platelet-derived growth factor (PDGF) is critical for the proliferation and migration of SMCs. Sunitinib [a PDGF receptor (PDGFR) tyrosine kinase inhibitor]-eluting stents may therefore inhibit neointimal formation. The aim of the present study was to examine the stent-based delivery of sunitinib in a rabbit carotid model; in addition, the effects of sunitinib were evaluated in vitro. Local administration of sunitinib markedly reduced neointimal formation without delaying re-endothelialization in the carotid artery model. In vitro, sunitinib inhibited SMC proliferation; however, no effects were observed on ECs. Sunitinib caused necrosis of SMCs. In addition, sunitinib attenuated PDGF-stimulated SMC migration in a scratch wound assay and inhibited α-SMA cytoskeleton polymerization. Furthermore, sunitinib inhibited PDGF-induced phosphorylation of extracellular signal-regulated kinase in vitro and in vivo. Therefore, this novel DES may be a potential strategy for the treatment of vascular disorders.
- Subjects
PLATELET-derived growth factor; SURGICAL stents; VASCULAR smooth muscle physiology; CAROTID artery; CYTOSKELETON; PHOSPHORYLATION; LABORATORY rabbits
- Publication
Molecular Medicine Reports, 2017, Vol 15, Issue 1, p21
- ISSN
1791-2997
- Publication type
Article
- DOI
10.3892/mmr.2016.5986