Effects of cerium oxide nanoparticles on hemostasis: Coagulation, platelets, and vascular endothelial cells

J Biomed Mater Res A. 2019 Jul;107(7):1551-1562. doi: 10.1002/jbm.a.36669. Epub 2019 Apr 17.

Abstract

Cerium oxide nanoparticles (nanoceria [NC]) have attracted much attention in biomedicine due to their surface composition that confers interesting redox activities and regenerative properties. Studies have demonstrated that the application of NPs in biomedicine can influence components of hemostatic system, inducing blood clotting, alterations of blood cells, and endothelial cell functions. NC were tested in vitro to assess their hemocompatibility and anticoagulant, anti-inflammatory, and anti-senescence activity in human endothelial cells. Hemocompatibility has been evaluated in vitro looking at the impact of NC on coagulation times, fibrinogen, and platelet aggregation. The effect of NC on vascular endothelial cells were assayed by testing cell viability, antioxidant activity, anticoagulant (tissue factor [TF]-mRNA expression) and anti-inflammatory properties (VCAM-1 exposure, cytokine release), and senescence (telomere shortening). NC did not show significant effects on coagulation process, hemolysis, or platelet aggregation. In endothelial cells, NC did not affect cell viability, reduced oxidative stress, inhibited mRNA-TF expression, VCAM-1 expression, and cytokine release. Moreover, NC reduce telomere shortening, possibly counteracting premature senescence. The hemocompatibility combined with anticoagulant and anti-inflammatory phenotype and the ability of counteract the premature senescence in vascular cells make NC a promising therapeutic tool in oxidative stress-related conditions. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A, 2019.

Keywords: coagulation; endothelial cells; hemocompatibility; nanoparticles; senescence.

MeSH terms

  • Antioxidants / pharmacology
  • Blood Coagulation* / drug effects
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism*
  • Cell Survival / drug effects
  • Cellular Senescence / drug effects
  • Cerium / pharmacology*
  • DNA / metabolism
  • Fluorescence
  • Hemolysis / drug effects
  • Hemostasis* / drug effects
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Human Umbilical Vein Endothelial Cells / ultrastructure
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Nanoparticles / chemistry*
  • Nanoparticles / ultrastructure
  • Platelet Aggregation / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reactive Oxygen Species / metabolism
  • Thromboplastin / genetics
  • Thromboplastin / metabolism
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antioxidants
  • Interleukin-6
  • Interleukin-8
  • RNA, Messenger
  • Reactive Oxygen Species
  • Vascular Cell Adhesion Molecule-1
  • Cerium
  • ceric oxide
  • DNA
  • Thromboplastin