Nickel ions from a corroded cardiovascular stent induce monocytic cell apoptosis: Proposed impact on vascular remodeling and mechanism

Chun-Ming Shih, Chun-Yao Huang, Li Rung Liao, Chiao Po Hsu, Nai-Wen Tsao, Hwai Shi Wang, Wei Yuan Chen, Yea Yang Su, Shing Jong Lin, Chun Che Shih, Feng-Yen Lin

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1088-1096
Number of pages9
JournalJournal of the Formosan Medical Association = Taiwan yi zhi
Volume114
Issue number11
DOIs
Publication statusPublished - Nov 1 2015

Keywords

  • Apoptosis
  • Corrosion
  • Monocyte
  • Nickel
  • Stent

ASJC Scopus subject areas

  • Medicine(all)

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