Huang Chen, Mei Haijun, Zhou Min, Zheng Xiaobing
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.
Mol Med Rep. 2017 Jan;15(1):21-28. doi: 10.3892/mmr.2016.5986. Epub 2016 Dec 5.
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.
一种新型药物洗脱支架（DES）需要靶向血管平滑肌细胞（SMC）而不损害内皮细胞（EC）。血小板衍生生长因子（PDGF）对SMC的增殖和迁移至关重要。因此，舒尼替尼[一种血小板衍生生长因子受体（PDGFR）酪氨酸激酶抑制剂]洗脱支架可能会抑制新生内膜形成。本研究的目的是在兔颈动脉模型中检测基于支架的舒尼替尼递送情况；此外，还在体外评估了舒尼替尼的作用。在颈动脉模型中，局部给予舒尼替尼可显著减少新生内膜形成，且不延迟再内皮化。在体外，舒尼替尼抑制SMC增殖；然而，对EC未观察到影响。舒尼替尼导致SMC坏死。此外，在划痕试验中，舒尼替尼减弱了PDGF刺激的SMC迁移，并抑制了α-SMA细胞骨架聚合。此外，舒尼替尼在体外和体内均抑制了PDGF诱导的细胞外信号调节激酶的磷酸化。因此，这种新型DES可能是治疗血管疾病的一种潜在策略。
