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首页> 外文期刊>Biomaterials >Suppression of post-angioplasty restenosis with an Akt1 siRNA-embedded coronary stent in a rabbit model
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Suppression of post-angioplasty restenosis with an Akt1 siRNA-embedded coronary stent in a rabbit model

机译：植入Akt1 siRNA的冠状动脉支架抑制血管成形术后再狭窄

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Restenosis is the formation of blockages occurring at the site of angioplasty or stent placement. In order to avoid such blockages, the suppression of smooth muscle cells near the implanted stent is required. The Akt1 protein is known to be responsible for cellular proliferation, and specific inhibition of Akt1 gene expression results in the retardation of cell growth. To take advantage of these benefits, we developed a new delivery technique for Akt1 siRNA nanoparticles from a hyaluronic acid (HA)-coated stent surface. For this purpose, the disulfide cross-linked low molecular polyethyleneimine (PEI) (ssPEI) was used as a gene delivery carrier because disulfide bonds are stable in an oxidative extracellular environment but degrade rapidly in reductive intracellular environments. In this study, Akt1 siRNA showed efficient ionic interaction with the ssPEI carrier, which was confirmed by polyacrylamide gel electrophoresis. Akt1 siRNA/ssPEI nanoparticles (ASNs) were immobilized on the HA-coated stent surface and exhibited stable binding and localization, followed by time-dependent sustained release for intracellular uptake. Cellular viability on the nanoparticle-immobilized surface was assessed using A10 vascular smooth muscle cells, and the results revealed that immobilized ASNs exhibited negligible cytotoxicity against the adhering A10 cells. Transfection efficiency was quantified using a luciferase assay; the transgene expression of Akt1 suppression through the delivered Akt1 siRNA was measured using RT-PCR and western blot, demonstrating higher gene silencing efficiency when compared to other carriers. ASN coated on HA stents were deployed in the balloon-injured external iliac artery in rabbits in vivo. It was shown that the Akt1 released from the stent suppressed the growth of the smooth muscle at the peri-stent implantation area, resulting in the prevention of restenosis in the post-implantation phase.
机译：再狭窄是在血管成形术或支架放置部位发生的阻塞形成。为了避免这种阻塞，需要抑制植入支架附近的平滑肌细胞。已知Akt1蛋白负责细胞增殖，并且对Akt1基因表达的特异性抑制导致细胞生长的延迟。为了利用这些好处，我们开发了一种从透明质酸（HA）涂层支架表面用于Akt1 siRNA纳米粒子的新递送技术。为此，将二硫键交联的低分子聚乙烯亚胺（PEI）（ssPEI）用作基因传递载体，因为二硫键在氧化性细胞外环境中稳定，但在还原性细胞内环境中迅速降解。在这项研究中，Akt1 siRNA显示出与ssPEI载体的有效离子相互作用，这已通过聚丙烯酰胺凝胶电泳得以证实。将Akt1 siRNA / ssPEI纳米颗粒（ASN）固定在HA涂层的支架表面上，并表现出稳定的结合和定位，然后随时间的持续释放进行细胞内摄取。使用A10血管平滑肌细胞评估了固定在纳米颗粒表面的细胞活力，结果表明，固定的ASN对粘附的A10细胞表现出可忽略的细胞毒性。使用萤光素酶测定法定量转染效率;使用RT-PCR和Western blot检测了通过传递的Akt1 siRNA抑制Akt1的转基因表达，与其他载体相比，其基因沉默效率更高。在体内，将涂在HA支架上的ASN部署在球囊损伤的外动脉中。结果表明，从支架释放的Akt1抑制了支架周围植入区域平滑肌的生长，从而防止了植入后阶段的再狭窄。

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