A novel PDGF receptor inhibitor-eluting stent attenuates in-stent neointima formation in a rabbit carotid model.
A novel PDGF receptor inhibitor-eluting stent attenuates in-stent neointima formation in a rabbit carotid model.
复制标题
一种新型 PDGF 受体抑制剂洗脱支架可减弱兔颈动脉模型中支架内新内膜的形成
DOI：
10.3892/mmr.2016.5986
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发表时间：
2017-01
影响因子：
3.4
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Huang C;Mei H;Zhou M;Zheng X
需要一种新型的药物洗脱支架(DES)来靶向血管平滑肌细胞(SMCs)而不损伤内皮细胞(ECs)。血小板衍生生长因子(PDGF)对SMC的增殖和迁移起着至关重要的作用。因此，舒尼替尼[一种PDGF受体(PDGFR)酪氨酸激酶抑制剂]洗脱支架可能会抑制新生内膜的形成。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的释放；此外，还在体外评估了舒尼替尼的作用。在颈动脉模型中，局部应用舒尼替尼可显著减少新生内膜的形成，而不会延迟再内皮化。在体外，舒尼替尼可抑制SMC的增殖，但对内皮细胞无影响。舒尼替尼可引起血管内皮细胞坏死。此外，在划痕实验中，舒尼替尼可减弱血小板衍生生长因子刺激的SMC迁移，并抑制α-SMA细胞骨架聚合。此外，苏尼替尼在体外和体内均能抑制PDGF诱导的细胞外信号调节激酶的磷酸化。因此，这种新型的DES可能是治疗血管疾病的一种潜在策略。
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.