Kir2.1 regulates rat smooth muscle cell proliferation, migration, and post-injury carotid neointimal formation
Kir2.1 regulates rat smooth muscle cell proliferation, migration, and post-injury carotid neointimal formation
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Kir2.1 调节大鼠平滑肌细胞增殖、迁移和损伤后颈动脉新生内膜形成
DOI：
10.1016/j.bbrc.2016.06.134
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发表时间：
2016
影响因子：
3.1
通讯作者：
Zhu Boqian
中科院分区：
文献类型：
--
作者：
Qiao Yong;Tang Chengchun;Wang Qingjie;Wang Dong;Yan Gaoliang;Zhu Boqian
血管平滑肌细胞（VSMC）从收缩型到合成型的表型转换是血管成形术后动脉粥样硬化和再狭窄等血管疾病的标志。在VSMC中发现了向内整流K+通道2.1 （Kir2.1）。然而，它是否在调节细胞转化中发挥功能作用仍不清楚。在这项研究中，我们评估了Kir2.1在VSMC增殖、迁移、表型转换和损伤后颈动脉内膜形成中的作用。Kir2.1敲低可显著抑制血小板源性生长因子bb刺激的大鼠血管平滑肌细胞（rat- vsmc）的增殖和迁移。在大鼠vsmc中，缺乏Kir2.1有助于平滑肌α-肌动蛋白、平滑肌22α和钙钙蛋白的恢复以及骨桥蛋白表达的降低。此外，他们的体内研究表明，大鼠颈动脉损伤后，vsmc转变为增生性表型，Kir2.1的下调显著抑制了颈动脉损伤后新内膜的形成。Kir2.1可能是治疗心血管疾病（如经皮冠状动脉介入治疗后的动脉粥样硬化和再狭窄）的潜在治疗靶点。
Phenotype switching of vascular smooth muscle cells (VSMC) from the contractile type to the synthetic type is a hallmark of vascular disorders such as atherosclerosis and restenosis after angioplasty. Inward rectifier K+channel 2.1 (Kir2.1) has been identified in VSMC. However, whether it plays a functional role in regulating cellular transformation remains obscure. In this study, we evaluated the role of Kir2.1 on VSMC proliferation, migration, phenotype switching, and post-injury carotid neointimal formation. Kir2.1 knockdown significantly suppressed platelet-derived growth factor BB-stimulated rat vascular smooth muscle cells (rat-VSMC) proliferation and migration. Deficiency in Kir2.1 contributed to the restoration of smooth muscle α-actin, smooth muscle 22α, and calponin and to a reduction in osteopontin expression in rat-VSMC. Moreover, thein vivostudy showed that rat-VSMC switched to proliferative phenotypes and that knockdown of Kir2.1 significantly inhibited neointimal formation after rat carotid injury. Kir2.1 may be a potential therapeutic target in the treatment of cardiovascular diseases, such as atherosclerosis and restenosis following percutaneous coronary intervention.