An essential role for stromal interaction molecule 1 in neointima formation following arterial injury
An essential role for stromal interaction molecule 1 in neointima formation following arterial injury
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基质相互作用分子 1 在动脉损伤后新内膜形成中的重要作用
DOI：
10.1093/cvr/cvn338
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发表时间：
2009-03-01
影响因子：
10.8
通讯作者：
Huang, Lan
中科院分区：
文献类型：
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作者：
Guo, Rui-Wei;Wang, Hong;Huang, Lan
有证据表明，基质相互作用分子1（stromal interaction molecule 1，STIM 1）作为内质网上的Ca 2+传感器发挥作用，导致信号转导至质膜并打开钙库操纵的Ca 2+通道（store-operated Ca 2 + channels，SOC）。SOC已在血管平滑肌细胞（VSMC）中被检测到，并被认为在收缩和细胞增殖的调节中具有重要作用。我们假设STIM 1的敲低抑制VSMC增殖和抑制新生内膜增生，我们使用大鼠球囊损伤模型和培养的大鼠主动脉VSMC检测STIM 1的敲低的效果。有趣的是，在大鼠颈动脉球囊损伤模型中，在损伤后14天，通过腺病毒递送小干扰RNA（siRNA）来敲低大鼠STIM 1显著抑制了新生内膜增生。人STIM 1在平滑肌中的重新表达逆转了STIM 1敲低对新生内膜形成的影响。大鼠主动脉VSMC用于体外测定。内源性STIM 1的敲低显著抑制VSMCs的增殖和迁移。此外，STIM 1敲低诱导细胞周期停滞在G 0/G1期，并导致SOC显着下降。补充与重组人STIM 1逆转siRNA敲低的效果。提示STIM 1在大鼠血管损伤后新生内膜形成中起重要作用，STIM 1可能成为预防血管介入术后再狭窄的新靶点。
There is evidence to suggest that stromal interaction molecule 1 (STIM1) functions as a Ca2+ sensor on the endoplasmic reticulum, leading to transduction of signals to the plasma membrane and opening of store-operated Ca2+ channels (SOC). SOC have been detected in vascular smooth muscle cells (VSMCs) and are thought to have an essential role in the regulation of contraction and cell proliferation. We hypothesized that knockdown of STIM1 inhibits VSMC proliferation and suppresses neointimal hyperplasia.We examined the effect of the knockdown of STIM1 using a rat balloon injury model and cultured rat aortic VSMCs. Interestingly, knockdown of rat STIM1 by adenovirus delivery of small interfering RNA (siRNA) significantly suppressed neointimal hyperplasia in a rat carotid artery balloon injury model at 14 days after injury. The re-expression of human STIM1 to smooth muscle reversed the effect of STIM1 knockdown on neointimal formation. Rat aortic VSMCs were used for the in vitro assays. Knockdown of endogenous STIM1 significantly inhibited proliferation and migration of VSMCs. Moreover, STIM1 knockdown induced cell-cycle arrest in G0/G1 and resulted in a marked decrease in SOC. Replenishment with recombinant human STIM1 reversed the effect of siRNA knockdown. These results suggest STIM1 has a critical role in neointimal formation in a rat model of vascular injury.STIM1 may represent a novel therapeutic target in the prevention of restenosis after vascular interventions.