Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress

Particle and Fibre Toxicology, Sep 2009

Air Pollution has been associated with significant adverse health effects leading to increased morbidity and mortality. Cumulative epidemiological and experimental data have shown that exposure to air pollutants lead to increased cardiovascular ischemic events and enhanced atherosclerosis. It appears that these associations are much stronger with the air particulate matter (PM) component and that in urban areas, the smaller particles could be more pathogenic, as a result of their greater propensity to induce systemic prooxidant and proinflammatory effects. Much is still unknown about the toxicology of ambient particulates as well as the pathogenic mechanisms responsible for the induction of adverse cardiovascular health effects. It is expected that better understanding of these effects will have large implications and may lead to the formulation and implementation of new regulatory policies. Indeed, we have found that ultrafine particles (<0.18 μm) enhance early atherosclerosis, partly due to their high content in redox cycling chemicals and their ability to synergize with known proatherogenic mediators in the promotion of tissue oxidative stress. These changes take place in parallel with increased evidence of phase 2 enzymes expression, via the electrophile-sensitive transcription factor, p45-NFE2 related transcription factor 2 (Nrf2). Exposure to ultrafine particles also results in alterations of the plasma HDL anti-inflammatory function that could be indicative of systemic proatherogenic effects. This article reviews the epidemiological, clinical and experimental animal evidence that support the association of particulate matter with atherogenesis. It also discusses the possible pathogenic mechanisms involved, the physicochemical variables that may be of importance in the greater toxicity exhibited by a small particle size, interaction with genes and other proatherogenic factors as well as important elements to consider in the design of future mechanistic studies. Extensive epidemiological evidence supports the association of air pollution with adverse health effects 123. It is increasingly being recognized that such effects lead to enhanced morbidity and mortality, mostly due to exacerbation of cardiovascular diseases and predominantly those of ischemic character 4. Indeed, in addition to the classical risk factors such as serum lipids, smoking, hypertension, aging, gender, family history, physical inactivity and diet, recent data have implicated air pollution as an important additional risk factor for atherosclerosis. This has been the subject of extensive reviews 56 and a consensus statement from the American Heart Association 7. This article reviews the supporting epidemiological and animal data, possible pathogenic mechanisms and future perspectives.

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Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress

Particle and Fibre Toxicology Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress Jesus A Araujo*1 and Andre E Nel*2 0 Division of Nanomedicine, Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA 90095 , USA 1 Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University of California , Los Angeles, CA 90095 , USA Air Pollution has been associated with significant adverse health effects leading to increased morbidity and mortality. Cumulative epidemiological and experimental data have shown that exposure to air pollutants lead to increased cardiovascular ischemic events and enhanced atherosclerosis. It appears that these associations are much stronger with the air particulate matter (PM) component and that in urban areas, the smaller particles could be more pathogenic, as a result of their greater propensity to induce systemic prooxidant and proinflammatory effects. Much is still unknown about the toxicology of ambient particulates as well as the pathogenic mechanisms responsible for the induction of adverse cardiovascular health effects. It is expected that better understanding of these effects will have large implications and may lead to the formulation and implementation of new regulatory policies. Indeed, we have found that ultrafine particles (<0.18 m) enhance early atherosclerosis, partly due to their high content in redox cycling chemicals and their ability to synergize with known proatherogenic mediators in the promotion of tissue oxidative stress. These changes take place in parallel with increased evidence of phase 2 enzymes expression, via the electrophile-sensitive transcription factor, p45-NFE2 related transcription factor 2 (Nrf2). Exposure to ultrafine particles also results in alterations of the plasma HDL anti-inflammatory function that could be indicative of systemic proatherogenic effects. This article reviews the epidemiological, clinical and experimental animal evidence that support the association of particulate matter with atherogenesis. It also discusses the possible pathogenic mechanisms involved, the physicochemical variables that may be of importance in the greater toxicity exhibited by a small particle size, interaction with genes and other proatherogenic factors as well as important elements to consider in the design of future mechanistic studies. Extensive epidemiological evidence supports the association of air pollution with adverse health effects [13]. It is increasingly being recognized that such effects lead to enhanced morbidity and mortality, mostly due to exacerbation of cardiovascular diseases and predominantly those of ischemic character [4]. Indeed, in addition to the classical risk factors such as serum lipids, smoking, hypertension, aging, gender, family history, physical inactivity and diet, recent data have implicated air pollution as an important additional risk factor for atherosclerosis. This has been the subject of extensive reviews [5,6] and a consensus statement from the American Heart Association [7]. This article reviews the supporting epidemiological and animal data, possible pathogenic mechanisms and future perspectives. - Exposure to air particulate matter leads to increased cardiovascular morbidity and mortality While air pollution is a complex mixture of compounds in gaseous (ozone, CO and nitrogen oxides) and particle phases [8], the strongest evidence among several hundred epidemiological studies linking air pollution with human health effects, centers around the particulate components [7-13]. Particulate matter (PM) is comprised of heterogenous compounds varying in size, number, chemical composition, surface area, concentration and source [7,8]. Some atmospheric particles are liquid, some are solid and others may contain a solid core surrounded by liquid. PM includes primary particles that are emitted directly from sources such as fossil-fuel combustion (e.g. diesel exhaust particles) and secondary particles that are generated from gases through chemical reactions involving atmospheric oxygen (O2), water vapor (H2O), reactive species such as ozone (O3), free radicals such as hydroxyl (.OH) and nitrate (.NO3) radicals, pollutants such as sulfur dioxide (SO2), nitrogen oxides (NOx), and organic gases from natural and anthropogenic sources [8]. Particles are also classified according to their aerodynamic diameter into size fractions such as PM10 ("thoracic" particles, < 10 m), PM2.5-10 ("coarse" particles, 2.5 to 10 m), PM2.5 (fine particles, < 2.5 m and UFP (ultrafine particles, < 0.1 m). These particles are derived from various sources and by various mechanisms as shown in Table 1, producing distinct lognormal modes in the particle size distributions by number and volume (nucleation, Aitken mode, accumulation and coarse modes) (Figure 1) [8]. Thoracic particles(PM10) Coarse particles(PM2.5-10) 2.5 - 10 Fine particles (PM2 (...truncated)


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Jesus A Araujo, Andre E Nel. Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress, Particle and Fibre Toxicology, 2009, pp. 24, 6, DOI: 10.1186/1743-8977-6-24