Cardiovascular Health Effects: Toxicity of Semi-Volatile and Nopn-Volatile Components of PM

摘要

Background: Evidence is needed to better understand the pollutant components and their sources responsible for associations between particle concentrations and cardiovascular outcomes. We previously found that atherosclerotic plaque formation was accelerated by exposure to quasi-ultrafine particle mass concentrations＜0.18 μm in diameter (PM_(0.18) in genetically modified (apoE-/-) mice. Particle-associated organic components, including polycyclic aromatic hydrocarbons (PAHs), had been demonstrated to elicit free radicals and promote oxidative stress which may contribute to the pathophysiology of coronary artery diseases. We therefore hypothesized that inhalation of ambient particles containing semivolatile organic compounds would accelerate development or worsening of atherosclerosis an exposed population and that removal of these constituents would mitigate the adverse effects. Methods: Genetically modified mice with deletions in the apoE gene (apoE-/-) were exposed to concentrated quasi-ultrafine ambient particles with aerodynamic diameters smaller than 0.18 μm (PM_(0.18); CAP) and to CAP which had been stripped of their semivolatile organic constituents using a thermal denuder (deCAP). Control apoE-/- mice were exposed to purified, filtered air. Exposures were performed in Los Angeles in a location proximal to two heavily trafficked roadways for 5 hr/day, 4 days/week for 8 weeks. Particle mass and number concentrations were measured during the exposures. Chemical analyses of the CAP and the collected semivolatile organics that had been stripped from the particles were made. Heart rate and heart rate variability (HRV) were measured using telemetry devices implanted in the mice before, during and after exposures. Following the last exposure, the mice were necropsied, biomarkers of oxidative stress and inflammation were measured and arterial plaque areas and wall thicknesses were determined. Results: Mice exposed to air and to deCAP showed minimal levels of arterial plaque formation and no significant changes in HRV after the 8 week exposure period. Mice exposed to CAP showed increased formation of arterial plaque, significantly markers of oxidative stress and decreased HRV. Findings in the CAP-exposed mice were statistically significantly more adverse than those observationed in air- or deCAP-exposed mice. Conclusions: Long term exposure to the quasi-ultrafine fraction of ambient PM is associated with increased oxidative stress, systemic inflammation, changes in autonomic cardiac control and accelerated formation of atherosclerotic plaque, but removal of the semivolatile organic constituents mitigates these toxic effects.