Apatinib (YN968D1) is a small‐molecule tyrosine kinase inhibitor（TKI）which can inhibit the activity of vascular endothelial growth factor receptor‐2 (VEGFR‐2). It has been reported that apatinib has anti‐tumour effect of inhibiting proliferation and inducing apoptosis of a variety of solid tumour cells, whereas its effect on vascular smooth muscle cells (VSMC) remains unclear. This study investigated the effect of apatinib on phenotypic switching of arterial smooth muscle cells in vascular remodelling. Compared to the vehicle groups, mice that were performed carotid artery ligation injury and treated with apatinib produced a reduction in abnormal neointimal area. For in vitro experiment, apatinib administration inhibited VSMC proliferation, migration and reversed VSMC dedifferentiation with the stimulation of platelet‐derived growth factor type BB (PDGF‐BB).In terms of mechanism, with the preincubation of apatinib, the activations of PDGF receptor‐β (PDGFR‐β) and phosphoinositide‐specific phospholipase C‐γ1 (PLC‐γ1) induced by PDGF‐BB were inhibited in VSMCs. With the preincubation of apatinib, the phosphorylation of PDGFR‐β, extracellular signal‐related kinases (ERK1/2) and Jun amino‐terminal kinases (JNK) induced by PDGF‐BB were also inhibited in rat vascular smooth muscle cell line A7r5. Herein, we found that apatinib attenuates phenotypic switching of arterial smooth muscle cells induced by PDGF‐BB in vitro and vascular remodelling in vivo. Therefore, apatinib is a potential candidate to treat vascular proliferative diseases.

中文翻译：

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阿帕替尼通过靶向PDGF受体-β来减弱血管重构中的动脉平滑肌细胞表型转换。

阿帕替尼（YN968D1）是一种小分子酪氨酸激酶抑制剂（TKI），可抑制血管内皮生长因子受体2（VEGFR-2）的活性。据报道，阿帕替尼具有抑制多种实体瘤细胞增殖和诱导其凋亡的抗肿瘤作用，而其对血管平滑肌细胞（VSMC）的作用尚不清楚。这项研究调查了阿帕替尼对血管重塑中动脉平滑肌细胞表型转换的影响。与媒介物组相比，遭受颈动脉结扎损伤并用阿帕替尼治疗的小鼠减少了异常的新内膜面积。对于体外实验，阿帕替尼给药可抑制VSMC增殖，血小板衍生生长因子BB型（PDGF-BB）的刺激迁移和逆转VSMC去分化从机制上讲，通过预孵育阿帕替尼，PDGF受体β（PDGFR-β）和磷酸肌醇磷脂酶的激活PDGF-BB诱导的C-γ1（PLC-γ1）在VSMC中受到抑制。通过预孵育阿帕替尼，PDGF-BB诱导的PDGFR-β，细胞外信号相关激酶（ERK1 / 2）和Jun氨基末端激酶（JNK）的磷酸化在大鼠血管平滑肌细胞系A7r5中也受到抑制。在本文中，我们发现阿帕替尼可减轻PDGF-BB诱导的动脉平滑肌细胞表型转换和体内血管重塑。因此，阿帕替尼是治疗血管增生性疾病的潜在候选者。通过预孵育阿帕替尼，VSMC中PDGF-BB诱导的PDGF受体-β（PDGFR-β）和磷酸肌醇特异性磷脂酶C-γ1（PLC-γ1）的激活受到抑制。通过预孵育阿帕替尼，PDGF-BB诱导的PDGFR-β，细胞外信号相关激酶（ERK1 / 2）和Jun氨基末端激酶（JNK）的磷酸化在大鼠血管平滑肌细胞系A7r5中也受到抑制。在本文中，我们发现阿帕替尼可减轻PDGF-BB诱导的动脉平滑肌细胞表型转换和体内血管重塑。因此，阿帕替尼是治疗血管增生性疾病的潜在候选者。通过预孵育阿帕替尼，VSMC中PDGF-BB诱导的PDGF受体-β（PDGFR-β）和磷酸肌醇特异性磷脂酶C-γ1（PLC-γ1）的激活受到抑制。通过预孵育阿帕替尼，PDGF-BB诱导的PDGFR-β，细胞外信号相关激酶（ERK1 / 2）和Jun氨基末端激酶（JNK）的磷酸化在大鼠血管平滑肌细胞系A7r5中也受到抑制。在本文中，我们发现阿帕替尼可减轻PDGF-BB诱导的动脉平滑肌细胞表型转换和体内血管重塑。因此，阿帕替尼是治疗血管增生性疾病的潜在候选者。PDGF-BB诱导的PDGFR-β，细胞外信号相关激酶（ERK1 / 2）和Jun氨基末端激酶（JNK）的磷酸化在大鼠血管平滑肌细胞A7r5中也受到抑制。在本文中，我们发现阿帕替尼可减轻PDGF-BB诱导的动脉平滑肌细胞表型转换和体内血管重塑。因此，阿帕替尼是治疗血管增生性疾病的潜在候选者。PDGF-BB诱导的PDGFR-β，细胞外信号相关激酶（ERK1 / 2）和Jun氨基末端激酶（JNK）的磷酸化在大鼠血管平滑肌细胞A7r5中也受到抑制。在本文中，我们发现阿帕替尼可减轻PDGF-BB诱导的动脉平滑肌细胞表型转换和体内血管重塑。因此，阿帕替尼是治疗血管增生性疾病的潜在候选者。