Vascular effects of nanoparticles in air pollution

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Vascular effects of nanoparticles in air pollution

Air pollution is responsible for several million deaths worldwide per year, predominantly through cardiovascular mortality. The nanoparticles in traffic exhaust are especially harmful, although the biological mechanisms by which they induce detrimental cardiovascular effects remain to be fully established.

Research from BHF Programme Grants (PI: Prof David Newby) demonstrated that controlled acute (1-2 h) exposure to dilute diesel exhaust (an especially rich source of combustion-derived nanoparticles) in man impaired the ability of forearm arteries to dilate; an effect that persisted for over 24 h. Subsequently, our group used animal models to establish that these effects were due to the particulate component of diesel exhaust.

We demonstrated that diesel exhaust particulate (DEP) can directly impair vascular function without the need for prior interaction with the pulmonary system or inflammatory cells. DEP adheres to the intimal surface of arteries (see Figure 1a), where it generates superoxide free radicals that impair relaxation through the scavenging of endothelium-derived nitric oxide (b). Pulmonary exposure to an Apolipoprotein-E knockout model demonstrated that DEP increased the size and complexity of atherosclerosis through generation of a systemic oxidative stress (c, d). This work was published in Environmental Health Perspectives and Particle and Fibre Toxicology.

Our group is now using these models to investigate which chemical constituents within DEP are causing these unwanted effects. Clean carbon particles (nCB; Figure 1b) have a limited capacity to induce vascular effects, suggesting that it is the surface chemicals on DEP that are responsible. We hypothesise that reactive transition metals and organic carbon species are driving these effects through redox-mediated reactions. Current work funded by BHF Special Project Grant (PI: Miller; SP/15/8/31575) will address other biological pathways, such as the role of eicosanoids as a mechanism by which inhalation of nanoparticles links the lung to the systemic circulation.