title: A novel PDGF receptor inhibitor-eluting stent attenuates in-stent neointima formation in a rabbit carotid model.
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.
authors.affiliation: Division of Vascular Surgery, Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Huang
authors.affiliation: Division of Vascular Surgery, Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Haijun
authors.initials: H
authors.lastname: Mei
authors.affiliation: Department of Vascular Surgery, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhou
authors.affiliation: Division of Vascular Surgery, Department of General Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu 226001, P.R. China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Zheng
mesh_terms: D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D002339:Carotid Arteries / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D054855:Drug-Eluting Stents; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007211:Indoles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D058426:Neointima / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D010766:Phosphorylation / Q000187:drug effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D011817:Rabbits; D017479:Receptors, Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015607:Stents / Q000009:adverse effects; D000077210:Sunitinib; D017539:Tunica Intima / Q000166:cytology / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; D017479:Receptors, Platelet-Derived Growth Factor; D000077210:Sunitinib