Zinc oxide nanoparticles induce migration and adhesion of monocytes to endothelial cells and accelerate foam cell formation

Toxicol Appl Pharmacol. 2014 Jul 1;278(1):16-25. doi: 10.1016/j.taap.2014.04.010. Epub 2014 Apr 16.

Abstract

Metal oxide nanoparticles are widely used in industry, cosmetics, and biomedicine. However, the effects of exposure to these nanoparticles on the cardiovascular system remain unknown. The present study investigated the effects of nanosized TiO2 and ZnO particles on the migration and adhesion of monocytes, which are essential processes in atherosclerogenesis, using an in vitro set-up of human umbilical vein endothelial cells (HUVECs) and human monocytic leukemia cells (THP-1). We also examined the effects of exposure to nanosized metal oxide particles on macrophage cholesterol uptake and foam cell formation. The 16-hour exposure to ZnO particles increased the level of monocyte chemotactic protein-1 (MCP-1) and induced the migration of THP-1 monocyte mediated by increased MCP-1. Exposure to ZnO particles also induced adhesion of THP-1 cells to HUVECs. Moreover, exposure to ZnO particles, but not TiO2 particles, upregulated the expression of membrane scavenger receptors of modified LDL and increased cholesterol uptake in THP-1 monocytes/macrophages. In the present study, we found that exposure to ZnO particles increased macrophage cholesterol uptake, which was mediated by an upregulation of membrane scavenger receptors of modified LDL. These results suggest that nanosized ZnO particles could potentially enhance atherosclerogenesis and accelerate foam cell formation.

Keywords: Adhesion; Atherosclerosis; Cholesterol uptake; Endotherial cells; Nanoparticles; Zinc oxide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Atherosclerosis / chemically induced
  • Atherosclerosis / metabolism
  • Atherosclerosis / pathology
  • Biological Transport
  • Cell Adhesion / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Cholesterol / metabolism
  • Coculture Techniques
  • Dose-Response Relationship, Drug
  • Foam Cells / drug effects*
  • Foam Cells / metabolism
  • Foam Cells / pathology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Human Umbilical Vein Endothelial Cells / pathology
  • Humans
  • Lipoproteins, LDL / metabolism
  • Metal Nanoparticles / toxicity*
  • Monocytes / drug effects*
  • Monocytes / metabolism
  • Monocytes / pathology
  • Particle Size
  • Receptors, Scavenger / drug effects
  • Receptors, Scavenger / metabolism
  • Time Factors
  • Titanium / toxicity
  • Zinc Oxide / toxicity*

Substances

  • Lipoproteins, LDL
  • Receptors, Scavenger
  • titanium dioxide
  • Cholesterol
  • Titanium
  • Zinc Oxide