Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers.
Potent suppression of vascular smooth muscle cell migration and human neointimal hyperplasia by KV1.3 channel blockers.
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DOI：
10.1093/cvr/cvq305
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发表时间：
2011-02-01
影响因子：
10.8
通讯作者：
Beech DJ
中科院分区：
文献类型：
--
作者：
Cheong A;Li J;Sukumar P;Kumar B;Zeng F;Riches K;Munsch C;Wood IC;Porter KE;Beech DJ
本研究的目的是确定KV 1钾通道阻滞剂作为人新生内膜增生抑制剂的潜力。从患者或小鼠获得血管，并在培养物中进行研究。逆转录聚合酶链反应和免疫细胞化学检测基因表达。全细胞膜片钳，细胞内钙测量，细胞迁移试验，和器官培养被用来评估通道功能。KV1.3是KV1通道中唯一的，当血管平滑肌细胞转换为增殖表型时，KV1通道显示出保留和上调的表达。在新生内膜形成中有强表达。增殖细胞的电压依赖性钾电流对三种不同的KV1.3通道阻断剂敏感。钙离子进入也受到抑制。所有三种阻滞剂都减少了血管平滑肌细胞迁移，并且效果是非累加的。其中一种阻断剂（margatoxin）非常有效，抑制细胞迁移，IC50为85 pM。在器官培养的人静脉样品中测试了两种阻断剂，它们都抑制了新生内膜增生。KV1.3钾通道在增殖小鼠和人血管平滑肌细胞中起作用，并对细胞迁移具有积极作用。通道阻断剂可用作新生内膜增生和其他不需要的血管重塑事件的抑制剂。
The aim of the study was to determine the potential for KV1 potassium channel blockers as inhibitors of human neoinitimal hyperplasia. Blood vessels were obtained from patients or mice and studied in culture. Reverse transcriptase–polymerase chain reaction and immunocytochemistry were used to detect gene expression. Whole-cell patch-clamp, intracellular calcium measurement, cell migration assays, and organ culture were used to assess channel function. KV1.3 was unique among the KV1 channels in showing preserved and up-regulated expression when the vascular smooth muscle cells switched to the proliferating phenotype. There was strong expression in neointimal formations. Voltage-dependent potassium current in proliferating cells was sensitive to three different blockers of KV1.3 channels. Calcium entry was also inhibited. All three blockers reduced vascular smooth muscle cell migration and the effects were non-additive. One of the blockers (margatoxin) was highly potent, suppressing cell migration with an IC50 of 85 pM. Two of the blockers were tested in organ-cultured human vein samples and both inhibited neointimal hyperplasia. KV1.3 potassium channels are functional in proliferating mouse and human vascular smooth muscle cells and have positive effects on cell migration. Blockers of the channels may be useful as inhibitors of neointimal hyperplasia and other unwanted vascular remodelling events.
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DOI：
10.1084/jem.177.3.637
发表时间：
1993-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
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影响因子：
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影响因子：
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发表时间：
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影响因子：
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影响因子：
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作者：
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