A novel PDGF receptor inhibitor-eluting stent attenuates in-stent neointima formation in a rabbit carotid model

Huang,Chen; Mei,Haijun; Zhou,Min; Zheng,Xiaobing

doi:10.3892/mmr.2016.5986

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
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Affiliations: Division of Vascular Surgery, Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China, Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
Published online on: December 5, 2016 https://doi.org/10.3892/mmr.2016.5986
Pages: 21-28
Copyright: © Huang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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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.

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