Large scale epidemiological studies suggest that inhaled ambient air pollution particles (PM10) may also have effects on the cardiovascular system. Small increases in particulate levels are associated with more cardiovascular deaths and hospital admissions in both time-series [94,95] and population studies [96,97]. Cohort studies have documented an association between elevated particulate and the onset of acute myocardial infarction [98,99], an increase in heart rate [100] and a decrease in heart rate variability [101]. Human chamber studies delivering concentrated ambient particles (CAPs) have confirmed that particulate can have direct effects on cardiovascular physiology with alterations in heart rate variability [101] and brachial artery diameter [102].
This CAPS work has not been able to discriminate which size fraction is responsible for any effects but the hypotheses relating to cardiovascular effects of CAPS (and PM in general) are as follows 1) particle-induced lung inflammation affects the endothelium, thrombotic potential, fibrinolytic balance and atheromatous plaque activity in ways that favour plaque rupture and thrombosis; 2) particles enter the interstitium and/or cause inflammation which affects the autonomic nerve endings that regulate the heart rhythm leading to dysrhythmia; 3) particles translocate to the blood and have direct effects on the endothelium, plaques and thrombogenic mechanism. In various models NP are shown to be highly potent in these three areas of effect i.e. NP are very potent at causing inflammation, they interstitialise readily and they can gain access to the blood. For these reasons CDNP, the principal NP in ambient air, are implicated in the cardiovascular effects of PM in these CAPS studies.
These studies address the population risks associated with ambient particulate, but do not allow any assessment of the contribution of individual air pollutants. In the Copenhagen Male Study the influence of occupational exposure on cardiovascular risk was assessed. In these men, 5 years or more of occupational exposure to welding fumes doubled the risk of myocardial infarction with exposure to solder and plastic fumes conferring similar increases in risk [103].
Figure 3 shows the two predominant mechanistic pathways hypothesised to mediate the adverse cardiovascular effects of CDNP [104,105]. On the right of Figure 3 inflammation caused by the CDNP is seen to affect the systemic inflammatory response and cause destabilisation of atheromatous plaques. On the left, bloodborne CDNP affect endothelial cells, platelets and plaques directly to enhance thrombogenesis.
CDNP are capable of eliciting an inflammatory response in the lung which could have stimulatory effects on leukocytes and other cells in the atherosclerotic plaques, leading to their rupture. This could occur is in the absence of any transfer of CDNP from the lungs to the circulation as it might rely on cytokines and other mediators which were released into the circulation in response to events in the lungs, affecting events in the plaques. However, CDNP could also have effects on the cardiovascular system by virtue of their ability to gain access to the bloodstream. This has been demonstrated in animal studies for a range of nanoparticles delivered by inhalation and instillation [106-111]. Once circulating, CDNP may interact with the vascular endothelium, or have direct effects on atherosclerotic plaques by entering them and causing local oxidative stress and pro-inflammatory effects similar to those caused in the lungs. Increased inflammation could destabilise the coronary plaque, resulting in rupture, thrombosis and acute coronary syndrome [104]. Furthermore, particles may interact with circulating coagulation factors to promote thrombogenesis. There is, as yet no published data demonstrating that the CDNP described here gain access to the blood in humans, but the animal studies suggest that this is a plausible hypothesis.
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