Associate editor: C.C.Y. PangThe pharmacology of particulate matter air pollution-induced cardiovascular dysfunction
Introduction
A correlation between air pollution and mortality was first revealed in the Meuse Valley air pollution episode on December 1930 in which 60 people died within 3 days in Engis, a town of 3500 inhabitants in Belgium (Nemery et al., 2001). Studies following the “London Fog” of December 1952 provided the first solid epidemiological data that air pollution increased mortality with an excess of 4000 deaths over a 2-week period of time (Logan, 1953). This disaster provided incontrovertible evidence that air pollution could kill, and has therefore attracted considerable attention from the scientific community. Since then numerous studies have supported the notion that the level of ambient pollution is an independent risk factor for cardiovascular and respiratory morbidity and mortality.
Air pollutants are a heterogeneous mixture of gases and particulate matter. The major gaseous components of air pollution are NO2, CO, SO2, and ozone. Particulate matter air pollution consists of solid and liquid particles derived from vehicle emissions, forest fires, industrial, domestic and agricultural pollutants. Particulate matter air pollution with an aerodynamic diameter of less than 10 μm is collectively known as PM10. A number of large epidemiological studies have shown that the particulate component of air pollution has the strongest association with adverse health effects (Pope et al., 1992, Dockery et al., 1993, Pope et al., 1995, Schwartz, 1999, Zanobetti et al., 2000, Hoek et al., 2001, Katsouyanni et al., 2001, Pope et al., 2004). Ambient PM10 is variable and complex in composition. It consists of various sizes of particles, transition metals and volatile organic compounds. Depending on its particle size, PM10 can be subdivided into coarse particles (PM2.5–PM10, diameter 2.5–10 μm); fine particles (PM2.5, diameter < 2.5 μm); and ultrafine particles (UFPs, diameter < 0.1 μm) (Fig. 1). Particles with larger diameters produced during crushing or grinding and from vehicles traveling on paved or unpaved roads tend to settle more quickly. Fine particles and UFPs remain suspended in the air for longer periods where they tend to aggregate into larger particles with the potential for their components to be altered before settling down. Particles derived from wood stoves, agricultural burning, forest fires and combustion of fossil fuel used in transportation, manufacturing and power generation are the main sources of fine particles and UFPs. Comparing to coarse particles, fine particles deposit in greater numbers and into deeper regions of the lungs due to their aerodynamic characteristics. Moreover, fine particles especially UFPs have a larger surface area and have been proposed to possess a much greater potential for interaction with biological targets, and consequently result in a more significant impact on health (Oberdorster et al., 1996, Nemmar et al., 1999).
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Cardiovascular morbidity and PM10 exposure
Exposure to air pollutant leads to increases in hospitalization due to cardiovascular diseases (Burnett et al., 1999, Schwartz, 1999, Hoek et al., 2001, Maheswaran et al., 2005a, Maheswaran et al., 2005b, Zanobetti and Schwartz, 2005). A study in 1985–1999 of 300,000 elderly residents of 21 US cities shows that a 10 μg/m3 increase of PM10 is associated with a significant increased risk of hospitalization for myocardial infarction (MI) (Burnett et al., 1999, Zanobetti and Schwartz, 2005). Kunzli
Hypotheses on how PM10 exposure induces vascular disease
Although strong evidence indicates that PM10 is an important independent risk factor (in addition to smoking, hypertension, hyperlipidemia and diabetes) for increased cardiovascular morbidity and mortality, the biological pathways by which ambient particles adversely affect cardiovascular function are unclear.
There are 2 broad hypotheses about how exposure to PM10 causes vascular disease. Seaton and colleagues in 1995 proposed that deposition of particles in the lung provoked a low-grade
Mechanisms of PM10-induced cardiovascular disease
Based on these 2 hypotheses, several biological pathways responsible for PM10-associated adverse cardiovascular outcomes have been explored, including (1) systemic inflammatory response induced by PM10 exposure that impacts blood vessels; (2) extra-pulmonary translocation of UFPs that activate vasculature; (3) reactive oxygen species (ROS) generated by particles that result in cardiovascular dysfunction; (4) endothelial dysfunction induced by the soluble and/or the particulate components of PM10
Conclusion
A large number of epidemiological and experimental studies have identified PM10 as an important new risk factor for the development and exacerbations of cardiovascular disease, and acts independently of known risk factors such as smoking, hypertension, hyperlipidemia and diabetes. However, the factors that determine and augment PM10-induced cardiovascular dysfunction are yet incomplete, and the understanding of the mechanisms leading to PM10-associated cardiovascular morbidity and mortality is
Acknowledgments
This work was generously supported by operating grants from the Heart and Stroke Foundation of Canada, Wolfe and Gina Churg Foundation, and the Canadian Institute for Health Research. Stephan F. van Eeden is an American Lung Association Career Investigator and the recipient of the William Thurlbeck Distinguish Research Award. Ni Bai is a recipient of a NSERC Scholarship.
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