Exposure to inhaled nickel nanoparticles causes a reduction in number and function of bone marrow endothelial progenitor cells

Abstract

Introduction: Particulate matter (PM), specifically nickel (Ni) found on or in PM, has been associated with an increased risk of mortality in human population studies and significant increases in vascular inflammation, generation of reactive oxygen species, altered vasomotor tone, and potentiated atherosclerosis in murine exposures. Recently, murine inhalation of Ni nanoparticles have been shown to cause pulmonary inflammation that affects cardiovascular tissue and potentiates atherosclerosis. These adverse cardiovascular outcomes may be due to the effects of Ni on endothelial progenitor cells (EPCs), endogenous semi-pluripotent stem cells that aid in endothelial repair. Thus, we hypothesize that Ni nanoparticle exposures decrease cell count and cause impairments in function that may ultimately have significant effects on various cardiovascular diseases, such as, atherosclerosis.

Methods: Experiments involving inhaled Ni nanoparticle exposures (2 days/5 h/day at ∼1200 µg/m³, 3 days/5 h/day at ∼700 µg/m³, and 5 days/5 h/day at ∼100 µg/m³), were performed in order to quantify bone marrow resident EPCs using flow cytometry in C57BL/6 mice. Plasma levels of human stromal cell-derived factor 1α (SDF-1α) and vascular endothelial growth factor (VEGF) were assessed by enzyme-linked immunosorbent assay and in vitro functional assessments of cultured EPCs were conducted.

Results and conclusions: Significant EPC count differences between exposure and control groups for Ni nanoparticle exposures were observed. Differences in EPC tube formation and chemotaxis were also observed for the Ni nanoparticle exposed group. Plasma VEGF and SDF-1α differences were not statistically significant. In conclusion, this study shows that inhalation of Ni nanoparticles results in functionally impaired EPCs and reduced number in the bone marrow, which may lead to enhanced progression of atherosclerosis.

Keywords::

• Nickel
• nanoparticles
• endothelial progenitor cell
• inhalation

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Correction to: Exposure to inhaled nickel nanoparticles causes a reduction in number and function of bone marrow endothelial progenitor cells