Over the last few decades it has become apparent that particles in air pollution have many detrimental effects in different organ systems. The cardiovascular effects of inhaled particles are especially important, given the high proportion of deaths attributed to air pollution that arise from cardiovascular causes. Our group has shown that exposure to diesel exhaust particles, an especially rich source of nanoparticles in urban air pollution, has multiple detrimental actions throughout the cardiovascular system; promoting blood clotting, impairing vascular function and exacerbating stress on the heart. However, the biological processes underlying the pulmonary exposure of particles and that of the cardiovascular system have yet to be fully established. This presentation describes a series of experimental studies in human subjects and preclinical models investigating whether nanoparticle translocation (the movement of particles from the lung into the circulation) could be an underlying pathway to account for the widespread cardiovascular actions of vehicle exhaust. Using gold nanoparticles as a model, we were able to demonstrate the presence of gold in the blood and urine within hours of inhalation in healthy volunteers. Furthermore, levels in the blood persisted for a number of months after the end of exposure. The translocation of gold nanoparticles was size-dependent, with smaller particles more readily entering the blood. Using a mouse model of atherosclerosis we demonstrated that translocated nanoparticles preferentially accumulated at areas of vascular disease. Finally, we demonstrated that inhaled particles reached areas of atherosclerosis in patients with a history of stroke. Particle translocation represents a convincing explanation for the multiple detrimental effects of inhaled nanoparticles, which could lead to increases in cardiovascular morbidity and mortality. These findings emphasise the need to reduce emissions from traffic as an important means to reduce the health effects of air pollution.
Physiology 2019 (Aberdeen, UK) (2019) Proc Physiol Soc 43, SA002
Research Symposium: From car to coronary: inhaled particles and the cardiovascular system
M. R. Miller1
1. Centre for Cardiovscular Science, University of Edinburgh, Edinburgh, Midlothian, United Kingdom.
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Where applicable, experiments conform with Society ethical requirements.