Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
J Appl Toxicol. 2021 Dec;41(12):1966-1979. doi: 10.1002/jat.4177. Epub 2021 May 6.
Despite advances in stent technology for vascular interventions, in-stent restenosis (ISR) remains a main complication. The corrosion of cobalt-chromium (CoCr) alloy coronary stents has been identified to be associated with ISR, whereas its role in ISR has not been elucidated. In the current work, CoCr nanoparticles, simulated corrosion products of CoCr alloy, were used to investigate their effect on the endothelial cells. It has been demonstrated that the cell viability declines and the cell membrane is damaged, indicating the cytotoxicity of CoCr nanoparticles. The expression of GRP78, CHOP, and cleaved-caspase12 proteins has increased when exposed to CoCr nanoparticles, suggesting that CoCr nanoparticles induced cell apoptosis through endoplasmic reticulum (ER) stress-mediated apoptotic pathway. An increased release of adhesion and inflammatory mediators was also induced by CoCr nanoparticles, including ICAM-1, VCAM-1, IL-1β, IL-6, and TNF-α. Our results demonstrated that CoCr nanoparticles could trigger apoptosis, adhesion, and inflammation. These findings indicated potential damaging effects of CoCr nanoparticles on the vascular endothelium, which suggested corrosion of CoCr alloy may promote the progression and development of ISR.
尽管血管介入治疗的支架技术取得了进展，但支架内再狭窄（ISR）仍然是主要并发症。已经确定钴铬（CoCr）合金冠状动脉支架的腐蚀与 ISR 有关，但其在 ISR 中的作用尚未阐明。在当前的工作中，使用 CoCr 纳米颗粒（CoCr 合金模拟腐蚀产物）来研究它们对内皮细胞的影响。结果表明，细胞活力下降，细胞膜受损，表明 CoCr 纳米颗粒具有细胞毒性。当暴露于 CoCr 纳米颗粒时，GRP78、CHOP 和 cleaved-caspase12 蛋白的表达增加，表明 CoCr 纳米颗粒通过内质网（ER）应激介导的凋亡途径诱导细胞凋亡。CoCr 纳米颗粒还诱导粘附和炎症介质的释放增加，包括 ICAM-1、VCAM-1、IL-1β、IL-6 和 TNF-α。我们的结果表明，CoCr 纳米颗粒可以触发细胞凋亡、粘附和炎症。这些发现表明 CoCr 纳米颗粒对血管内皮具有潜在的损伤作用，这表明 CoCr 合金的腐蚀可能促进 ISR 的进展和发展。
