Background/Purpose: Monocytes play important roles in inflammatory responses and vascular remodeling after vascular stenting. This research focused on impacts of nickel (Ni) ions released from a corroded cardiovascular stent on cytotoxicity and monocyte activation. Methods: A human promonocytic (macrophage-like) cell line (U937) was exposed to graduated concentrations of Ni2+ in vitro. Cells were observed and harvested at indicated times to determine the effects using histological and biochemical methods. Results: Ni caused U937 cell death in dose- and time-dependent manners. In vitro, high concentrations of Ni2+ (>240 μM) significantly induced cell apoptosis and increased terminal deoxynucleotidyl transferase (TdT) dUTP nick end labeling (TUNEL)-positive cells according to flow cytometric surveillance and triggered apoptotic cell death. Although no significant changes in Bcl-2 or Bax expressions were detected after 24 hours of Ni2+ treatment, increasing cleavage of caspase-3 and -8 was present. Results showed that cleavage of caspase-8 was inhibited by the presence of the inhibitor, Z-IETD-FMK, and this suggested the presence of Ni2+-induced U937 cell death through a death receptor-mediated pathway. Simultaneously, when treated with a high concentration of Ni2+ ions, expressions of the vascular remodeling factors, matrix metalloproteinases (MMP)-9 and -2, were activated in dose- and time-dependent manners. Secretion of the proliferative factor, monocyte chemoattractant protein (MCP)-1, significantly increased during the first 6 hours of incubation with 480 μM Ni2+-treated medium. Conclusion: Our results demonstrated that a high concentration of Ni ions causes apoptotic cell death of circulating monocytes. They may also play different roles in vascular remodeling during the corrosion process following implantation of Ni alloy-containing devices.
|頁（從 - 到）||1088-1096|
|期刊||Journal of the Formosan Medical Association = Taiwan yi zhi|
|出版狀態||已發佈 - 十一月 1 2015|
ASJC Scopus subject areas
Shih, C-M., Huang, C-Y., Liao, L. R., Hsu, C. P., Tsao, N-W., Wang, H. S., Chen, W. Y., Su, Y. Y., Lin, S. J., Shih, C. C., & Lin, F-Y. (2015). Nickel ions from a corroded cardiovascular stent induce monocytic cell apoptosis: Proposed impact on vascular remodeling and mechanism. Journal of the Formosan Medical Association = Taiwan yi zhi, 114(11), 1088-1096. https://doi.org/10.1016/j.jfma.2014.03.007