The acute exposure effects of inhaled nickel nanoparticles on murine endothelial progenitor cells

<div><p></p><p><i>Introduction</i>: The discovery of endothelial progenitor cells (EPCs) may help to explain observed cardiovascular effects associated with inhaled nickel nanoparticle exposures, such as increases in vascular inflammation, generation of reactive oxygen species, altered vasomotor tone and potentiated atherosclerosis in murine species.</p><p><i>Methods</i>: Following an acute whole body inhalation exposure to 500 µg/m³ of nickel nanoparticles for 5 h, bone marrow EPCs from C57BL/6 mice were isolated. EPCs were harvested for their RNA or used in a variety of assays including chemotaxis, tube formation and proliferation. Gene expression was assessed for important receptors involved in EPC mobilization and homing using RT-PCR methods. EPCs, circulating endothelial progenitor cells (CEPCs), circulating endothelial cells (CECs) and endothelial microparticles (EMPs) were quantified on a BD FACSCalibur to examine endothelial damage and repair associated with the exposure.</p><p><i>Results and conclusions</i>: Acute exposure to inhaled nickel nanoparticles significantly increased both bone marrow EPCs as well as their levels in circulation (CEPCs). CECs were significantly elevated indicating that endothelial damage occurred due to the exposure. There was no significant difference in EMPs between the two groups. Tube formation and chemotaxis, but not proliferation, of bone marrow EPCs was impaired in the nickel nanoparticle exposed group. These results coincided with a decrease in the mRNA of receptors involved in EPC mobilization and homing. These data provide new insight into how an acute nickel nanoparticle exposure to half of the current Occupational Safety & Health Administration (OSHA) permissible exposure limit may adversely affect EPCs and exacerbate cardiovascular disease states.</p></div

The basic characteristics of the male participants.

<p>The basic characteristics of the male participants.</p

The basic characteristics of the female participants.

<p>The basic characteristics of the female participants.</p

The relationship between visceral adiposity index and blood pressure levels in females.

<p>The relationship between visceral adiposity index and blood pressure levels in females.</p

The Role of Metal Components in the Cardiovascular Effects of PM_2.5

<div><p>Exposure to ambient fine particulate matter (PM_2.5) increases risks for cardiovascular disorders (CVD). However, the mechanisms and components responsible for the effects are poorly understood. Based on our previous murine exposure studies, a translational pilot study was conducted in female residents of Jinchang and Zhangye, China, to test the hypothesis that specific chemical component of PM_2.5 is responsible for PM_2.5 associated CVD. Daily ambient and personal exposures to PM_2.5 and 35 elements were measured in the two cities. A total of 60 healthy nonsmoking adult women residents were recruited for measurements of inflammation biomarkers. In addition, circulating endothelial progenitor cells (CEPCs) were also measured in 20 subjects. The ambient levels of PM_2.5 were comparable between Jinchang and Zhangye (47.4 and 54.5µg/m³, respectively). However, the levels of nickel, copper, arsenic, and selenium in Jinchang were 82, 26, 12, and 6 fold higher than Zhangye, respectively. The levels of C-reactive protein (3.44±3.46 vs. 1.55±1.13), interleukin-6 (1.65±1.17 vs. 1.09±0.60), and vascular endothelial growth factor (117.6±217.0 vs. 22.7±21.3) were significantly higher in Jinchang. Furthermore, all phenotypes of CEPCs were significantly lower in subjects recruited from Jinchang than those from Zhangye. These results suggest that specific metals may be important components responsible for PM_2.5-induced cardiovascular effects and that the reduced capacity of endothelial repair may play a critical role.</p> </div

Differences in daily ambient exposures between Jinchang and Zhangye from March 6^th to April 4^th, 2010.

<p>Panel A: PM_2.5 Mass Concentrations; Panel B: Nickel Mass Concentrations; Panel C: Fold differences in concentrations of 35 elements between Jinchang over Zhangye.</p

Percent excess risk from the mean values of biomarkers per inter-quartile-range increase in

<p>: 1) risk factors and air pollution in univariate regression model. “Jinchang” is an indicator (Jinchang=1; Zhangye=0). Metal concentrations are log-transformed (Panel A); 2) PM2.5 and selected metals, adjusting for age, cotinine level, BMI, blood sugar, LDL, HDL, triglycerides, systolic and diastolic blood pressure. Metal concentrations are log-transformed (Panel B). </p