Heart Failure Reviews

, Volume 22, Issue 3, pp 337–347 | Cite as

The mechanisms of air pollution and particulate matter in cardiovascular diseases

  • Antonella Fiordelisi
  • Prisco Piscitelli
  • Bruno Trimarco
  • Enrico Coscioni
  • Guido Iaccarino
  • Daniela SorrientoEmail author


Clinical and epidemiological studies demonstrate that short- and long-term exposure to air pollution increases mortality due to respiratory and cardiovascular diseases. Given the increased industrialization and the increased sources of pollutants (i.e., cars exhaust emissions, cigarette smoke, industry emissions, burning of fossil fuels, incineration of garbage), air pollution has become a key public health issue to solve. Among pollutants, the particulate matter (PM) is a mixture of solid and liquid particles which differently affects human health depending on their size (i.e., PM10 with a diameter <10 μm reach the lung and PM2.5 with a diameter <2.5 μm penetrate deeper into the lung). In particular, the acute exposure to PM10 and PM2.5 increases the rate of cardiovascular deaths. Thus, appropriate interventions to reduce air pollution may promote great benefits to public health by reducing the risk of cardiovascular diseases. Several biological mechanisms have been identified to date which could be responsible for PM-dependent adverse cardiovascular outcomes. Indeed, the exposure to PM10 and PM2.5 induces sustained oxidative stress and inflammation. PM2.5 is also able to increase autonomic nervous system activation. Some potential therapeutic approaches have been tested both in pre-clinical and clinical studies, based on the intake of antioxidants from dietary or by pharmacological administration. Studies are still in progress to increase the knowledge of PM activation of intracellular pathways and propose new strategies of intervention.


Air pollution Particulate matter Acute cardiovascular diseases Chronic cardiovascular diseases Oxidative stress 


Air pollution is the introduction of harmful substances into the atmosphere and has adverse effects on human health [1]. These substances (i.e., carbon, nitrogen and sulfur oxides, heavy metals, ozone and photochemical oxidants, toxic pollutants) can be solid particles, liquid droplets, or gasses suspended in the air which vary in size, composition, and origin. They can have a natural origin (volcanoes and dust storms) or be man-made (power plants and industrial processes, vehicular traffic, domestic coal burning, industrial and municipal waste incinerators) [2, 3, 4, 5, 6]. Given the variety of sources of air pollution, the concentration of pollutants in the air can change from area to area, also depending on meteorological factors, such as wind speed and direction. The extent of the effects on human health depends on pollutant’s concentration and time of exposure. Indeed, young children and elderly people should be less exposed compared with working adults who often move around different cities. People working in industries are likely the most exposed to chemical toxic compounds or hazardous fumes. Clinical and epidemiological studies have already ascertained that air pollution increases respiratory and cardiovascular mortality [1]. For this reason, it is fundamental to increase the knowledge about the molecular mechanisms by which pollutants affect human health, in order to develop effective therapeutic strategies, and to reduce the emission of pollutants in the air, to limit their effects on health.

The particulate matter

Among the pollutants which can harm human health, here, we focus on the particulate matter (PM) since the increase of its concentration in the air increases the risk of cardiopulmonary and lung cancer mortality [7, 8]. PM is the sum of all solid and liquid particles suspended in the air which came from different sources and are different in chemical composition and size. Depending on its sources, PM can be classified into “primary particles,” which are emitted directly from a source (construction sites, unpaved roads, fields, smokestacks or fires) and “secondary particles,” which can form in complicated reactions of chemicals (sulfur dioxides and nitrogen oxide) that are emitted into the atmosphere from power plants, industries, and automobiles [9, 10].

Primary PM sources are derived from both human (agricultural operations, industrial processes, combustion of wood and fossil fuels, construction and demolition activities, and entrainment of road dust into the air) and natural activities (windblown dust and wildfires). The composition of PM varies in time and space (transition metals, ions, organic compound, quinoid stable radicals of carbonaceous material, minerals, reactive gasses, and materials of biologic origin), and this attributes to PM a different toxicity [11]. Moreover, small particles can absorb and retain toxic substances, which are responsible for lung cell impairment [12]. The deposition of inhaled particles in the respiratory tract depends mainly on breathing pattern and aerodynamic particle size. Particles larger than 10 μm (PM50) are filtered through the nose but they are too large to reach the respiratory tract. Thus, PM50 can be trapped in the mucus lining within the nose and can be easily eliminated through normal breathing activities. Particles smaller than 10 μm can reach the lung (thoracic particles, PM10) and are deposited in the nasal cavities and upper airways with nasal breathing. In this latter group, fine particles (PM2.5), with a diameter <2.5 μm, and ultrafine particles (UFP), with a diameter <0.1 μm, can penetrate deeper into the lungs and deposit in alveolar regions during mouth breathing. PM2.5 can also be absorbed into the bloodstream through alveolar capillaries causing lung and systemic inflammation [9, 10, 12]. Total lung deposition of these particles is about 60% for ultrafine particles and 20% for fine particles [13]. In adults at rest, the nasal deposition of PM2.5 is about 20% and increases to 30–40% during exercise. Lower values (about 10–20%) are reached in children aged 5–15 years [13]. Once deposited in the lung, most particles are removed through several clearance mechanisms. Insoluble particles deposited on ciliated airways are generally removed from the respiratory tract by mucociliary activity within 24–48 h [14]. The clearance from the pulmonary region is usually rapid and may occur through the action of alveolar macrophages, whose removal from the lungs can instead take several weeks [15]. In a polluted environment, in a 24-h period, each lung acinus could receive approximately 30 million particles and each alveolus 1500 particles. Lung airways and alveoli retain 50% of these particles which are mostly composed by PM2.5 [16]. PM2.5 is also the 96% of effectively retained particles in the lung parenchyma [17].

Epidemiological studies and data from animal models indicate that particle pollution exposure affects health and that, in particular, the cardiovascular and the respiratory system are affected primarily [18, 19, 20, 21]. However, the function of several other organs can be also influenced. Moreover, several epidemiological and clinical evidences suggest that PM2.5 and PM10 are associated with increased hospitalization [8, 22, 23] and mortality due to cardiovascular disease [24], especially in persons with congestive heart failure, frequent arrhythmias, or both [25].

Pollution effects on cardiovascular diseases

Cardiovascular diseases (CVD) are actually among the main causes of death in the world [26, 27]. They have a multifactorial etiology and, based on their clinical presentation, can be divided into chronic (i.e., heart failure and hypertension) and acute (i.e., acute myocardial infarction and arrhythmia) conditions.

Several pieces of evidence indicate that air pollutants, and in particular PM, seriously affect the cardiovascular system. Indeed, the inhalation of PM, especially PM2.5 and PM10, promotes cardiovascular events occurring within hours or days after exposure [28]. The heart and the vascular system are highly vulnerable to short-term and long-term exposure to PM2.5, especially in association with aging and existing coronary or structural heart diseases [29]. Accordingly, a cohort study estimates that a short-term exposure to PM2.5 increases the risk of cardiovascular events from 0.4 to 1.0% [14]. A multicity study, including data from Europe, the USA, and Canada, demonstrated that a 10-μg/m3 increase in PM10 is associated with an enhanced rate of mortality with larger effects in Canada [30]. This study suggests higher effects of PM10 on daily mortality in cities with a higher temperature and a larger contribution of traffic emissions to PM. In the Air Pollution and Health: a European Approach (APHEA) project, an increase of sulfur dioxide (SO2) and PM10 was associated with 0.4% increase in the rate of cardiovascular mortality in major European cities [31]. Thus, both PM2.5 and PM10 concentrations are closely associated with cardiovascular diseases, and PM2.5 seems to be a larger determinant of adverse health effects compared with PM10. These effects have been demonstrated in both acute and chronic cardiovascular (CV) diseases in response to short- and long-term exposure to PM as described below.

Several studies demonstrate that short-term exposure to PM can trigger acute cardiovascular events (myocardial infarction, stroke) and long-term exposure increased this risk of heart failure [14].

Acute effects of pollution on CV diseases

The short-term exposure to PM mainly affects acute cardiovascular diseases such as myocardial infarction (MI) and cardiac arrhythmia. An increased risk of MI has been reported in association with short-term exposure to PM2.5 [32]. In particular, it has been found that increased concentrations of PM2.5 are associated with an increased risk of ST-segment elevation myocardial infarction (STEMI). However, no associations have been found with non-ST-segment elevation myocardial infarction (NSTEMI) [43]. This could be the result of the rupture of larger plaque and promotion of thrombus formation in patients with STEMI in response to PM2.5 compared with patients with NSTEMI [43]. Elevated concentrations of fine particles in the air may transiently elevate the risk of MI within a few hours and 1 day after exposure [33]. Also, an increase of PM10 levels is associated with an increased risk of MI in elderly patients [34]. Indeed, a multicity case-crossover study demonstrates that in elderly residents of 21 US cities, a 0.65% increased risk of hospitalization for MI exists per 10-μg/m3 increase in ambient PM10 concentration. The mechanisms for acute, short-term exposure PM-dependent myocardial ischemic injury can be attributed to increased systemic inflammation, altered endothelial function, and enhanced thrombotic tendency, as demonstrated in mouse and dog models of myocardial ischemia [35, 36]. Short PM exposure is also associated with atrial fibrillation (AF). Indeed, in patients with known cardiac disease, PM2.5 is an acute trigger of AF, since it is able within hours to induce a 26% increase of odds of AF for each 6.0-mg/m3 increase in PM2.5 concentration [37]. Sudden cardiac death and cardiac arrhythmias are related to the activity of the autonomic nervous system, that can be measure by changes in the heart rate variability (HRV). It has been shown that the indoor exposure to PM2.5 and household activities cause acute changes in HRV indices among housewives [38].

Chronic effects of pollution on CV diseases

A recent prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE project shows that long-term exposure to PM is associated with the incidence of coronary events. In particular, a 5-μg/m3 increase in estimated annual mean PM2.5 and a 10-μg/m3 increase in estimated annual mean PM10 are associated with a 13 and 12%, respectively, increased risk of coronary events. This association persists also at low levels of exposure, below the current European limit values (25 μg/m3 for PM2.5, 40 μg/m3 for PM10) [39]. The American Cancer Society (ACS) cohort study demonstrated that prolonged exposure to PM2.5 is associated with heart failure-dependent death and hospitalizations [40]. Accordingly, the reduction of PM2.5 exposure reduced heart failure admissions [41]. However, also, short-term exposure is associated with daily admissions for heart failure [42]. It has been demonstrated that inhalation of air pollutants, such as PM2.5 and black carbon, could favor the development of cardiometabolic disorders, including hypertension [43, 44, 45, 46]. In particular, within a typical Chinese global megacity, 1- to 7-day exposure to PM2.5 is significantly associated with the elevation of systolic blood pressure, ranging from 2.0 to 2.7 mmHg [47]. Increased systemic blood pressure and vasoconstriction due to short-term exposure to PM could lead to increased cardiac afterload and risk of acute decompensated heart failure [48]. Also, long-term exposure to PM2.5 increases the risk of mortality for heart failure [8]. Indeed, fine PM exposure is strongly associated with mortality due to ischemic heart disease, heart failure, and cardiac arrest. For these cardiovascular causes of death, a 10-μg/m3 elevation in fine PM was associated with 8 to 18% increases in mortality risk. A long-term PM2.5 exposure is associated with increased corrected QT duration, a risk factor for arrhythmia [49], in elderly patients. This suggests that the effects of PM on cardiovascular events may be mediated, in part, by changes in cardiac repolarization [50, 51].

In literature, there is poor research referring specifically to the effects of PM in individuals with pre-existing cardiovascular conditions [33, 52, 53]. Furthermore, the few clinical studies that have investigated this matter propose discordant results, probably due to differences in composition and concentration of PM in the cities where the studies were performed, and/or the confounding effect of other pollutant, such as smoking. In patients with myocardial infarction, the inhalation of PM leads to an adverse ventricular remodeling and worsening of myocardial fibrosis [54].

All these findings suggest that an association exists between PM2.5 exposure and acute/chronic CV diseases, and that it is dependent on particles concentration and time of exposure.

Potential biological mechanisms

The link between PM and cardiovascular disease is clearly established but the mechanisms whereby this association exists remain to be fully elucidated. Different potential mechanisms have been hypothesized that can be activated by direct effects of pollutants on the cardiovascular system, blood, and lung receptors or by indirect effects due to pulmonary oxidative stress and inflammatory responses (Fig. 1) [9]. In addition, alterations of the autonomic tone might contribute to the instability of a vascular plaque and initiation of cardiac arrhythmias (Fig. 1). The direct effects of air pollution could be responsible for the acute cardiovascular responses to PM exposure, such as myocardial infarction. The indirect effects, instead, contribute to a systemic inflammatory state, which in turn activates chronic responses impairing vascular function and accelerating atherosclerosis.
Fig. 1

PM target tissues. PM can affect cardiovascular system by different potential mechanisms: direct or indirect lung inflammation, direct blood translocation, and autonomic regulation

Direct translocation into circulation

PM can cross the pulmonary epithelium into the circulation or interact with lung receptors (direct effects) to induce an acute cardiovascular response. The first evidence derives from studies of Nemmar, which demonstrates that ultrafine particles and PM2.5 could translocate into the pulmonary circulation and the systemic circulation [55, 56]. To date, two mechanisms have been described by which PM exposure causes direct cardiovascular dysfunction: reactive oxygen species (ROS) production and regulation of calcium levels.

Indeed, it is known that ROS have a key role in both physiology and pathophysiology of the heart. Moderate ROS production is protective in response to myocardium ischemia [57] but excessive levels induce cell damage which in turn leads to the development of cardiovascular diseases [58]. It is now validated that increased ROS production has also a key role in PM-induced vascular cytotoxicity [59] and cardiac myocyte dysfunction [60, 61]. The oxidative stress induced by a PM-dependent ROS production can also affect vascular function, and PM exposure has been associated with arterial vasoconstriction, by disrupting endothelial vasodilation and endogenous fibrinolysis through ROS [62]. On the other hand, calcium (Ca2+) is vital for cardiomyocyte function, and it is essential for excitation-contraction coupling and regulation of contractile strength [63, 64, 65]. PM-induced peroxide production affects calcium regulation of the Na+-Ca2+ exchange protein [66] and L-type Ca2+ channel protein [67]. These events increase the concentration of cytosolic calcium and reduce sarcoplasmic reticulum stores of the ion. The consequence is the reduced cardiac contractility and the increased Ca2+-activated nuclear signaling which lead to hypertrophy (Fig. 2).
Fig. 2

PM induces cardiovascular dysfunction by ROS production and Ca2+ release. PM causes direct cardiovascular dysfunction by two different mechanisms: ROS production and regulation of calcium levels. Indeed, PM induces an increase of ROS production and an increase in cytosolic calcium. The increase of ROS production affects vascular function, and the increased of Ca2+ levels activates nuclear signaling associated with hypertrophy. Moreover, the combination of oxidative stress and increased Ca2+ levels induced by PM exposure causes mitochondrial dysfunction

The combination of oxidative stress and increased Ca2+ levels induced by PM exposure causes the opening of the mitochondrial permeability transition pore (MTP), leading to reduced mitochondrial membrane polarization and to induced mitochondrial respiration (Fig. 2) [68, 69]. Finally, PM inhibits nitric oxide synthase activity and nitric oxide release into the bloodstream favoring vasoconstriction (Fig. 3) [70].
Fig. 3

Effects of PM in endothelial cells. PM exposure inhibits nitric oxide synthase activity and nitric oxide release into the bloodstream favoring vasoconstriction

Pulmonary oxidative stress and systemic inflammation

It is shown that inhaled pollutants can induce pulmonary oxidative stress/inflammation (indirect effects) that contribute to a systemic inflammatory state which in turn activates hemostatic pathways, impairs vascular function, and accelerates atherosclerosis [71]. This finding has been validated both in vitro [72] and in vivo [42, 73].

One hypothesized mechanism includes pollution-induced lung damage by oxidative stress and inflammation that leads to lung dysfunction, respiratory distress, and cardiovascular disease which are potentially related to hypoxemia [74]. PM is inhaled and enters the lung and deposits on the alveoli, causing an inflammatory response that leads to an increase of circulating proinflammatory biomarkers (C-reactive protein, fibrinogen) and native immune response [43, 45, 46, 74, 75]. A recent in vivo study demonstrated that after PM2.5 exposure for 2 h, a rapid increase of reactive oxygen species generation occurred in the hearts and lungs of rats [44]. Oxidative stress activates specific transcription factors (NF-kappaB and AP-1), which in turn upregulate the expression of genes coding for cytokines, chemokines, and other proinflammatory mediators (Fig. 4). These latter induce the systemic inflammation [76] which leads to the increase of the common carotid artery intima-media thickness and an increase of coronary calcification [77, 78] on one hand but also favors atheromatous plaque destabilization and rupture, and thrombus formation which in turn induce acute events [79]. It has been demonstrated that PM2.5 alone does not alter blood pressure but in response to angiotensin II, the exposure to PM2.5 potentiates hypertension through NAD(P)H oxidase- and eNOS-dependent ROS generation [80]. This, in turn, activates the Rho/ROCK signaling pathway that is a key regulator of vascular smooth muscle tone through its effects on calcium sensitization of the contractile apparatus and is implicated in the pathogenesis of hypertension [80]. Accordingly, it has been suggested that the activation of TLR4 and NADPH oxidase in monocyte/macrophages by oxidized phospholipids may represent one potential mechanism by which PM2.5 mediates systemic inflammation [81].
Fig. 4

PM-dependent systemic inflammation in the lungs. PM exposure induces a rapid increase of reactive oxygen species generation. Oxidative stress activates a specific transcription factor, NF-kappaB, which in turn upregulates the expression of genes coding for proinflammatory mediators. These latter induce a systemic inflammation which favors atheromatous plaque destabilization and rupture and endothelial dysfunction

Disturbance of the autonomic nervous system

The autonomic nervous system has a key role in the control of heart rate (HR) and heart rate variability (HRV), the two predictors of cardiac death in HF [82]. It has been shown that the autonomic nervous system is involved in the pathophysiology of PM-induced cardiopulmonary diseases. Indeed, PM affects HRV, resting HR, and blood pressure, suggesting an activation of the sympathetic drive [79, 83]. HRV decreases rapidly in response to PM exposure [25, 84, 85, 86, 87] due to a decreased parasympathetic input to the heart. This unleashes the activation of the sympathetic drive and increases the incidence of cardiac arrhythmia and the risk of cardiovascular morbidity and mortality [79]. A similar observation also indicates an alternative pathway of SNS activation by showing that fine particulate induces alveolar inflammation, leading to the release of potentially harmful cytokines and the decrease of HRV [88].

It seems that PM exposure alters heart rate control by the autonomic nervous system (ANS) through an increase in systolic blood pressure. Indeed, the chronic exposure to fine PM increases plasma levels of angiotensin II, a potent vasoconstrictor, leading to an increase in blood pressure [89].

Potential therapeutic approaches

It is well established that PM induces oxidative stress by increasing ROS production [90]. Moreover, several diseases are characterized by chronic inflammation and antioxidant deficiency [91] that might increase the susceptibility to the additional oxidative stress caused by air pollution exposure. In this context, antioxidant therapy could be useful to counteract this phenomenon as shown both in vitro and in vivo [92, 93, 94, 95, 96, 97, 98, 99].

Animal studies

Data from animal models suggest that a range of antioxidant compounds can prevent the effects of air pollution, both in vitro and in vivo [92, 93, 94, 95, 96, 97, 98, 99]. It has been shown that fine PM exposure significantly impairs cardiovascular functions by decreasing circulating endothelial progenitor cells (EPCs) [92]. Indeed, PM treatment in mice significantly decreased circulating EPC population, promoted their apoptosis, increased ROS production, and increased serum levels of TNF-α and IL-1β [92]. The treatment with the antioxidant N-acetylcysteine (NAC) or the overexpression of antioxidant enzyme network (AON), that is composed of superoxide dismutase SOD1, SOD3, and glutathione peroxidase (Gpx-1), could effectively reverse this phenomenon [92]. This finding suggests that antioxidants are effective to reduce the adverse effects of PM on EPCs.

Accordingly, NAC had a protective effect on inflammatory response and oxidative stress damage in rats exposed to coal dust [95], and rescued changes in heart rate and the decrease in HRV in rats exposed to urban air particles [96]. Besides pharmacological interventions, antioxidant mechanisms could also be increased by dietary habits since diet is their major source. Indeed, it has been shown that several nutrients (vitamin C, vitamin E, β-carotene, omega-3 fatty acids, vitamin A, and folic acid) in supplementation studies are able to regulate the effects of air pollutants or modulate the immune response [98, 99, 100, 101].

Human studies

Although it is clear that antioxidants are useful for the treatment of PM-induced oxidative stress in animal models, in humans, they seem to be less effective or have long-term side effects. Indeed, several clinical trials have reported no benefit from vitamin E supplementation on coronary heart disease probably due to its effectiveness only at the early stage of the disease [94].

β-Carotene is one of the most widely studied carotenoids for both its pro-vitamin A activity and its abundance in fruits and vegetables [93]. In the last decade, high-dose supplementation with carotenoids or vitamin A has been used successfully in the treatment of oxidative stress in chronic diseases [97]. Moreover, carotenoids reduce the cardiovascular risk by lowering blood pressure, inflammatory cytokines, and markers of inflammation (such as C-reactive protein), and by increasing insulin sensitivity in tissues [93]. However, in a few clinical studies, harmful effects have been observed in response to β-carotene and vitamin A, such as the higher incidence of lung cancer in smokers [102]. Thus, antioxidant vitamins and micronutrients might have the potential to counteract PM effects on human health but further studies are needed with prolonged follow-up or with lower doses of antioxidants to evaluate long-term side effects.

Several studies show that the intake of n-3 PUFA from dietary or a pharmacological supplementation decreases the risk of mortality due to coronary heart disease [103] even if only a few studies have demonstrated the effect of this antioxidant on cardiac function in response to air pollution [104]. In a randomized trial, the supplementation with fish oil significantly decreased the effect of PM2.5 on HRV [104]. In additions to antioxidant-based therapy, it has been shown that statins attenuate PM-dependent reduction of HRV in subjects lacking the GSTM1 allele and that are therefore genetically susceptible to oxidative stress [105].


The short- and long-term exposure to PM contributes to the development and progression of acute and chronic CV diseases. PM can easily enter into the respiratory system and contributes to the development of cardiovascular events by inducing a systemic inflammatory condition or affecting the autonomic nervous system. Given the continuous variability of air pollution, that is associated with the evolution of the technological progress, and individual movements through numerous microenvironments every day, it is not surprising that data from air pollution studies could be very variable. This could limit the ability to significantly link health outcomes with single pollutant and requires, in future studies, the use of new tools to better measure the full air pollution mix and to better quantify the effects of exposure and the toxic combinations of the different pollutants. Appropriate interventions to reduce air pollution may promote great benefits to public health by reducing the risk of CV diseases. Several interventions have been carried out in the last decades which have significantly ameliorated air pollutant exposure in public places. Indeed, the introduction of smoking bans in public places and the new generation of cars with a reduced CO2 emission have been useful to reduce the exposure to air pollutants and consequently the incidence of cardiovascular diseases. Besides these interventions, it is also important to better understand the mechanisms by which air pollution induces damage to the cardiovascular system since this will allow the development of new therapeutic approaches.



This study was supported by grants from “BEYONDSILOS, FP7-ICT-PCP,” “Campania Bioscience, PON03PE_00060_8,” and PRIN 2015EASE8Z_003.

Compliance with ethical standards

Ethical standards

The manuscript does not contain clinical studies or patient data.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Brunekreef B, Holgate ST (2002) Air pollution and health. Lancet 360(9341):1233–1242. doi: 10.1016/S0140-6736(02)11274-8 PubMedCrossRefGoogle Scholar
  2. 2.
    Blumenthal I (2001) Carbon monoxide poisoning. J R Soc Med 94(6):270–272PubMedPubMedCentralGoogle Scholar
  3. 3.
    Chen TM, Gokhale J, Shofer S, Kuschner WG (2007) Outdoor air pollution: nitrogen dioxide, sulfur dioxide, and carbon monoxide health effects. The American journal of the medical sciences 333(4):249–256. doi: 10.1097/MAJ.0b013e31803b900f PubMedCrossRefGoogle Scholar
  4. 4.
    Tchounwou PB, Yedjou CG, Patlolla AK, Sutton DJ (2012) Heavy metal toxicity and the environment. EXS 101:133–164. doi: 10.1007/978-3-7643-8340-4_6 PubMedPubMedCentralGoogle Scholar
  5. 5.
    Garcia-Algar O, Zapater M, Figueroa C, Vall O, Basagana X, Sunyer J, Freixa A, Guardino X, Pichini S (2003) Sources and concentrations of indoor nitrogen dioxide in Barcelona, Spain. J Air Waste Manage Assoc 53(11):1312–1317CrossRefGoogle Scholar
  6. 6.
    Wainman T, Zhang J, Weschler CJ, Lioy PJ (2000) Ozone and limonene in indoor air: a source of submicron particle exposure. Environ Health Perspect 108(12):1139–1145PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Miller KA, Siscovick DS, Sheppard L, Shepherd K, Sullivan JH, Anderson GL, Kaufman JD (2007) Long-term exposure to air pollution and incidence of cardiovascular events in women. N Engl J Med 356(5):447–458. doi: 10.1056/NEJMoa054409 PubMedCrossRefGoogle Scholar
  8. 8.
    Pope CA 3rd, Burnett RT, Thun MJ, Calle EE, Krewski D, Ito K, Thurston GD (2002) Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 287(9):1132–1141PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Brook RD, Franklin B, Cascio W, Hong Y, Howard G, Lipsett M, Luepker R, Mittleman M, Samet J, Smith SC Jr, Tager I, Expert Panel on P, Prevention Science of the American Heart A (2004a) Air pollution and cardiovascular disease: a statement for healthcare professionals from the Expert Panel on Population and Prevention Science of the American Heart Association. Circulation 109(21):2655–2671. doi: 10.1161/01.CIR.0000128587.30041.C8 PubMedCrossRefGoogle Scholar
  10. 10.
    Miller MR, Shaw CA, Langrish JP (2012) From particles to patients: oxidative stress and the cardiovascular effects of air pollution. Futur Cardiol 8(4):577–602. doi: 10.2217/fca.12.43 CrossRefGoogle Scholar
  11. 11.
    Valavanidis A, Fiotakis K, Vlachogianni T (2008) Airborne particulate matter and human health: toxicological assessment and importance of size and composition of particles for oxidative damage and carcinogenic mechanisms. Journal of environmental science and health Part C, Environmental carcinogenesis & ecotoxicology reviews 26(4):339–362. doi: 10.1080/10590500802494538 CrossRefGoogle Scholar
  12. 12.
    Ni L, Chuang CC, Zuo L (2015) Fine particulate matter in acute exacerbation of COPD. Front Physiol 6:294. doi: 10.3389/fphys.2015.00294 PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Becquemin MH, Swift DL, Bouchikhi A, Roy M, Teillac A (1991) Particle deposition and resistance in the noses of adults and children. Eur Respir J 4(6):694–702PubMedGoogle Scholar
  14. 14.
    Schlesinger RB (1990) The interaction of inhaled toxicants with respiratory tract clearance mechanisms. Crit Rev Toxicol 20(4):257–286. doi: 10.3109/10408449009089865 PubMedCrossRefGoogle Scholar
  15. 15.
    Pepelko WE (1987) Feasibility of dose adjustment based on differences in long-term clearance rates of inhaled particulate matter in humans and laboratory animals. Regulatory toxicology and pharmacology: RTP 7(3):236–252PubMedCrossRefGoogle Scholar
  16. 16.
    Brown DM, Wilson MR, MacNee W, Stone V, Donaldson K (2001) Size-dependent proinflammatory effects of ultrafine polystyrene particles: a role for surface area and oxidative stress in the enhanced activity of ultrafines. Toxicol Appl Pharmacol 175(3):191–199. doi: 10.1006/taap.2001.9240 PubMedCrossRefGoogle Scholar
  17. 17.
    Churg A, Brauer M (1997) Human lung parenchyma retains PM2.5. Am J Respir Crit Care Med 155(6):2109–2111. doi: 10.1164/ajrccm.155.6.9196123 PubMedCrossRefGoogle Scholar
  18. 18.
    Cohen AJ, Ross Anderson H, Ostro B, Pandey KD, Krzyzanowski M, Kunzli N, Gutschmidt K, Pope A, Romieu I, Samet JM, Smith K (2005) The global burden of disease due to outdoor air pollution. Journal of toxicology and environmental health Part A 68(13–14):1301–1307. doi: 10.1080/15287390590936166 PubMedCrossRefGoogle Scholar
  19. 19.
    Huang YC, Ghio AJ (2006) Vascular effects of ambient pollutant particles and metals. Curr Vasc Pharmacol 4(3):199–203PubMedCrossRefGoogle Scholar
  20. 20.
    Kunzli N, Tager IB (2005) Air pollution: from lung to heart. Swiss Med Wkly 135(47–48):697–702 doi: 2005/47/smw-11025 PubMedGoogle Scholar
  21. 21.
    Sharma RK, Agrawal M (2005) Biological effects of heavy metals: an overview. J Environ Biol 26(2 Suppl):301–313PubMedGoogle Scholar
  22. 22.
    Pope CA 3rd, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, Godleski JJ (2004a) Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circulation 109(1):71–77. doi: 10.1161/01.CIR.0000108927.80044.7F PubMedCrossRefGoogle Scholar
  23. 23.
    Samet JM, Dominici F, Curriero FC, Coursac I, Zeger SL (2000) Fine particulate air pollution and mortality in 20 U.S. cities, 1987–1994. N Engl J Med 343(24):1742–1749. doi: 10.1056/NEJM200012143432401 PubMedCrossRefGoogle Scholar
  24. 24.
    Smith SC Jr, Blair SN, Bonow RO, Brass LM, Cerqueira MD, Dracup K, Fuster V, Gotto A, Grundy SM, Miller NH, Jacobs A, Jones D, Krauss RM, Mosca L, Ockene I, Pasternak RC, Pearson T, Pfeffer MA, Starke RD, Taubert KA (2001) AHA/ACC Scientific Statement: AHA/ACC guidelines for preventing heart attack and death in patients with atherosclerotic cardiovascular disease: 2001 update: a statement for healthcare professionals from the American Heart Association and the American College of Cardiology. Circulation 104(13):1577–1579PubMedCrossRefGoogle Scholar
  25. 25.
    Peters A, Doring A, Wichmann HE, Koenig W (1997) Increased plasma viscosity during an air pollution episode: a link to mortality? Lancet 349(9065):1582–1587. doi: 10.1016/S0140-6736(97)01211-7 PubMedCrossRefGoogle Scholar
  26. 26.
    Mathers CD, Sadana R, Salomon JA, Murray CJ, Lopez AD (2001) Healthy life expectancy in 191 countries, 1999. Lancet 357(9269):1685–1691. doi: 10.1016/S0140-6736(00)04824-8 PubMedCrossRefGoogle Scholar
  27. 27.
    Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Magid D, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER, Moy CS, Mussolino ME, Nichol G, Paynter NP, Schreiner PJ, Sorlie PD, Stein J, Turan TN, Virani SS, Wong ND, Woo D, Turner MB, American Heart Association Statistics C, Stroke Statistics S (2013) Executive summary: heart disease and stroke statistics—2013 update: a report from the American Heart Association. Circulation 127(1):143–152. doi: 10.1161/CIR.0b013e318282ab8f PubMedCrossRefGoogle Scholar
  28. 28.
    Tofler GH, Muller JE (2006) Triggering of acute cardiovascular disease and potential preventive strategies. Circulation 114(17):1863–1872. doi: 10.1161/CIRCULATIONAHA.105.596189 PubMedCrossRefGoogle Scholar
  29. 29.
    Pope CA 3rd, Muhlestein JB, May HT, Renlund DG, Anderson JL, Horne BD (2006) Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution. Circulation 114(23):2443–2448. doi: 10.1161/CIRCULATIONAHA.106.636977 PubMedCrossRefGoogle Scholar
  30. 30.
    Samoli E, Peng R, Ramsay T, Pipikou M, Touloumi G, Dominici F, Burnett R, Cohen A, Krewski D, Samet J, Katsouyanni K (2008) Acute effects of ambient particulate matter on mortality in Europe and North America: results from the APHENA study. Environ Health Perspect 116(11):1480–1486. doi: 10.1289/ehp.11345 PubMedPubMedCentralCrossRefGoogle Scholar
  31. 31.
    Katsouyanni K, Touloumi G, Spix C, Schwartz J, Balducci F, Medina S, Rossi G, Wojtyniak B, Sunyer J, Bacharova L, Schouten JP, Ponka A, Anderson HR (1997) Short-term effects of ambient Sulphur dioxide and particulate matter on mortality in 12 European cities: results from time series data from the APHEA project. Air Pollution and Health: a European approach. BMJ 314(7095):1658–1663PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Mustafic H, Jabre P, Caussin C, Murad MH, Escolano S, Tafflet M, Perier MC, Marijon E, Vernerey D, Empana JP, Jouven X (2012) Main air pollutants and myocardial infarction: a systematic review and meta-analysis. JAMA 307(7):713–721. doi: 10.1001/jama.2012.126 PubMedCrossRefGoogle Scholar
  33. 33.
    Peters A, Dockery DW, Muller JE, Mittleman MA (2001a) Increased particulate air pollution and the triggering of myocardial infarction. Circulation 103(23):2810–2815PubMedCrossRefGoogle Scholar
  34. 34.
    Zanobetti A, Schwartz J (2005) The effect of particulate air pollution on emergency admissions for myocardial infarction: a multicity case-crossover analysis. Environ Health Perspect 113(8):978–982PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Cozzi E, Hazarika S, Stallings HW 3rd, Cascio WE, Devlin RB, Lust RM, Wingard CJ, Van Scott MR (2006) Ultrafine particulate matter exposure augments ischemia-reperfusion injury in mice. Am J Phys Heart Circ Phys 291(2):H894–H903. doi: 10.1152/ajpheart.01362.2005 Google Scholar
  36. 36.
    Bartoli CR, Wellenius GA, Coull BA, Akiyama I, Diaz EA, Lawrence J, Okabe K, Verrier RL, Godleski JJ (2009) Concentrated ambient particles alter myocardial blood flow during acute ischemia in conscious canines. Environ Health Perspect 117(3):333–337. doi: 10.1289/ehp.11380 PubMedCrossRefGoogle Scholar
  37. 37.
    Link MS, Luttmann-Gibson H, Schwartz J, Mittleman MA, Wessler B, Gold DR, Dockery DW, Laden F (2013) Acute exposure to air pollution triggers atrial fibrillation. J Am Coll Cardiol 62(9):816–825. doi: 10.1016/j.jacc.2013.05.043 PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    Huang YL, Chen HW, Han BC, Liu CW, Chuang HC, Lin LY, Chuang KJ (2014) Personal exposure to household particulate matter, household activities and heart rate variability among housewives. PLoS One 9(3):e89969. doi: 10.1371/journal.pone.0089969 PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Cesaroni G, Forastiere F, Stafoggia M, Andersen ZJ, Badaloni C, Beelen R, Caracciolo B, de Faire U, Erbel R, Eriksen KT, Fratiglioni L, Galassi C, Hampel R, Heier M, Hennig F, Hilding A, Hoffmann B, Houthuijs D, Jockel KH, Korek M, Lanki T, Leander K, Magnusson PK, Migliore E, Ostenson CG, Overvad K, Pedersen NL, J JP, Penell J, Pershagen G, Pyko A, Raaschou-Nielsen O, Ranzi A, Ricceri F, Sacerdote C, Salomaa V, Swart W, Turunen AW, Vineis P, Weinmayr G, Wolf K, de Hoogh K, Hoek G, Brunekreef B, Peters A (2014) Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project. BMJ 348:f7412. doi: 10.1136/bmj.f7412 PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Pope CA, Burnett RT, Thurston GD, Thun MJ, Calle EE, Krewski D, Godleski JJ (2004b) Cardiovascular mortality and long-term exposure to particulate air pollution—epidemiological evidence of general pathophysiological pathways of disease. Circulation 109(1):71–77. doi: 10.1161/01.Cir.0000108927.80044.7f PubMedCrossRefGoogle Scholar
  41. 41.
    Dominici F, Peng RD, Bell ML, Pham L, McDermott A, Zeger SL, Samet JM (2006) Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA 295(10):1127–1134. doi: 10.1001/jama.295.10.1127 PubMedPubMedCentralCrossRefGoogle Scholar
  42. 42.
    Costa DL, Dreher KL (1997) Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models. Environ Health Perspect 105(Suppl 5):1053–1060PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Ghio AJ, Kim C, Devlin RB (2000) Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers. Am J Respir Crit Care Med 162(3):981–988PubMedCrossRefGoogle Scholar
  44. 44.
    Gurgueira SA, Lawrence J, Coull B, Murthy GGK, Gonzalez-Flecha B (2002) Rapid increases in the steady-state concentration of reactive oxygen species in the lungs and heart after particulate air pollution inhalation. Environ Health Perspect 110(8):749–755PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Pekkanen J, Brunner EJ, Anderson HR, Tiittanen P, Atkinson RW (2000) Daily concentrations of air pollution and plasma fibrinogen in London. Occup Environ Med 57(12):818–822PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Peters A, Frohlich M, Doring A, Immervoll T, Wichmann HE, Hutchinson WL, Pepys MB, Koenig W (2001b) Particulate air pollution is associated with an acute phase response in men—results from the MONICA-Augsburg Study. Eur Heart J 22(14):1198–1204. doi: 10.1053/euhj.2000.2483 PubMedCrossRefGoogle Scholar
  47. 47.
    Brook RD, Sun Z, Brook JR, Zhao X, Ruan Y, Yan J, Mukherjee B, Rao X, Duan F, Sun L, Liang R, Lian H, Zhang S, Fang Q, Gu D, Sun Q, Fan Z, Rajagopalan S (2016) Extreme air pollution conditions adversely affect blood pressure and insulin resistance: the air pollution and cardiometabolic disease study. Hypertension 67(1):77–85. doi: 10.1161/HYPERTENSIONAHA.115.06237 PubMedCrossRefGoogle Scholar
  48. 48.
    Wold LE, Ying Z, Hutchinson KR, Velten M, Gorr MW, Velten C, Youtz DJ, Wang A, Lucchesi PA, Sun Q, Rajagopalan S (2012a) Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution. Circ Heart Fail 5(4):452–461. doi: 10.1161/CIRCHEARTFAILURE.112.966580 PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Mordukhovich I, Kloog I, Coull B, Koutrakis P, Vokonas P, Schwartz J (2016) Association between particulate air pollution and QT interval duration in an elderly cohort. Epidemiology 27(2):284–290. doi: 10.1097/Ede.0000000000000424 PubMedPubMedCentralGoogle Scholar
  50. 50.
    Brook RD, Rajagopalan S, Pope CA, Brook JR, Bhatnagar A, Diez-Roux AV, Holguin F, Hong YL, Luepker RV, Mittleman MA, Peters A, Siscovick D, Smith SC, Whitsel L, Kaufman JD, Epidemiol AHAC, Dis CKC, Metab CNPA (2010) Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 121(21):2331–2378. doi: 10.1161/CIR.0b013e3181dbece1 PubMedCrossRefGoogle Scholar
  51. 51.
    Henneberger A, Zareba W, Ibald-Mulli A, Ruckerl R, Cyrys J, Couderc JP, Mykins B, Woelke G, Wichmann HE, Peters A (2005) Repolarization changes induced by air pollution in ischemic heart disease patients. Environ Health Perspect 113(4):440–446. doi: 10.1289/ehp.7579 PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Sullivan J, Ishikawa N, Sheppard L, Siscovick D, Checkoway H, Kaufman J (2003) Exposure to ambient fine particulate matter and primary cardiac arrest among persons with and without clinically recognized heart disease. Am J Epidemiol 157(6):501–509PubMedCrossRefGoogle Scholar
  53. 53.
    Peters A, Liu E, Verrier RL, Schwartz J, Gold DR, Mittleman M, Baliff J, Oh JA, Allen G, Monahan K, Dockery DW (2000) Air pollution and incidence of cardiac arrhythmia. Epidemiology 11(1):11–17PubMedCrossRefGoogle Scholar
  54. 54.
    Wold LE, Ying ZK, Hutchinson KR, Velten M, Gorr MW, Velten C, Youtz DJ, Wang AX, Lucchesi PA, Sun QH, Rajagopalan S (2012b) Cardiovascular remodeling in response to long-term exposure to fine particulate matter air pollution. Circulation-Heart Failure 5(4):452–461. doi: 10.1161/Circheartfailure.112.966580 PubMedPubMedCentralCrossRefGoogle Scholar
  55. 55.
    Nemmar A, Vanbilloen H, Hoylaerts MF, Hoet PH, Verbruggen A, Nemery B (2001) Passage of intratracheally instilled ultrafine particles from the lung into the systemic circulation in hamster. Am J Respir Crit Care Med 164(9):1665–1668. doi: 10.1164/ajrccm.164.9.2101036 PubMedCrossRefGoogle Scholar
  56. 56.
    Nemmar A, Hoet PH, Vanquickenborne B, Dinsdale D, Thomeer M, Hoylaerts MF, Vanbilloen H, Mortelmans L, Nemery B (2002) Passage of inhaled particles into the blood circulation in humans. Circulation 105(4):411–414PubMedCrossRefGoogle Scholar
  57. 57.
    Zhu X, Zuo L (2013) Characterization of oxygen radical formation mechanism at early cardiac ischemia. Cell Death Dis 4:e787. doi: 10.1038/cddis.2013.313 PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    He F, Zuo L (2015) Redox roles of reactive oxygen species in cardiovascular diseases. Int J Mol Sci 16(11):27770–27780. doi: 10.3390/ijms161126059 PubMedPubMedCentralCrossRefGoogle Scholar
  59. 59.
    Bai Y, Suzuki AK, Sagai M (2001) The cytotoxic effects of diesel exhaust particles on human pulmonary artery endothelial cells in vitro: role of active oxygen species. Free Radic Biol Med 30(5):555–562PubMedCrossRefGoogle Scholar
  60. 60.
    Okayama Y, Kuwahara M, Suzuki AK, Tsubone H (2006) Role of reactive oxygen species on diesel exhaust particle-induced cytotoxicity in rat cardiac myocytes. Journal of toxicology and environmental health Part A 69(18):1699–1710. doi: 10.1080/15287390600631078 PubMedCrossRefGoogle Scholar
  61. 61.
    Zuo L, Youtz DJ, Wold LE (2011) Particulate matter exposure exacerbates high glucose-induced cardiomyocyte dysfunction through ROS generation. PLoS One 6(8):e23116. doi: 10.1371/journal.pone.0023116 PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Mills NL, Tornqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE (2005) Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation 112(25):3930–3936. doi: 10.1161/CIRCULATIONAHA.105.588962 PubMedCrossRefGoogle Scholar
  63. 63.
    Louch WE, Ferrier GR, Howlett SE (2002) Changes in excitation-contraction coupling in an isolated ventricular myocyte model of cardiac stunning. Am J Phys Heart Circ Phys 283(2):H800–H810. doi: 10.1152/ajpheart.00020.2002 Google Scholar
  64. 64.
    Ter Keurs HE, Boyden PA (2007) Calcium and arrhythmogenesis. Physiol Rev 87(2):457–506. doi: 10.1152/physrev.00011.2006 PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Morgan JP (1991) Abnormal intracellular modulation of calcium as a major cause of cardiac contractile dysfunction. N Engl J Med 325(9):625–632. doi: 10.1056/NEJM199108293250906 PubMedCrossRefGoogle Scholar
  66. 66.
    Coetzee WA, Ichikawa H, Hearse DJ (1994) Oxidant stress inhibits Na-Ca-exchange current in cardiac myocytes: mediation by sulfhydryl groups? Am J Phys 266(3 Pt 2):H909–H919Google Scholar
  67. 67.
    Chiamvimonvat N, O'Rourke B, Kamp TJ, Kallen RG, Hofmann F, Flockerzi V, Marban E (1995) Functional consequences of sulfhydryl modification in the pore-forming subunits of cardiovascular Ca2+ and Na+ channels. Circ Res 76(3):325–334PubMedCrossRefGoogle Scholar
  68. 68.
    Xia T, Korge P, Weiss JN, Li N, Venkatesen MI, Sioutas C, Nel A (2004) Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity. Environ Health Perspect 112(14):1347–1358PubMedPubMedCentralCrossRefGoogle Scholar
  69. 69.
    Bernardi P (1999) Mitochondrial transport of cations: channels, exchangers, and permeability transition. Physiol Rev 79(4):1127–1155PubMedGoogle Scholar
  70. 70.
    Muto E, Hayashi T, Yamada K, Esaki T, Sagai M, Iguchi A (1996) Endothelial-constitutive nitric oxide synthase exists in airways and diesel exhaust particles inhibit the effect of nitric oxide. Life Sci 59(18):1563–1570PubMedCrossRefGoogle Scholar
  71. 71.
    Suwa T, Hogg JC, Quinlan KB, Ohgami A, Vincent R, van Eeden SF (2002) Particulate air pollution induces progression of atherosclerosis. J Am Coll Cardiol 39(6):935–942PubMedCrossRefGoogle Scholar
  72. 72.
    Kennedy T, Ghio AJ, Reed W, Samet J, Zagorski J, Quay J, Carter J, Dailey L, Hoidal JR, Devlin RB (1998) Copper-dependent inflammation and nuclear factor-kappaB activation by particulate air pollution. Am J Respir Cell Mol Biol 19(3):366–378. doi: 10.1165/ajrcmb.19.3.3042 PubMedCrossRefGoogle Scholar
  73. 73.
    Brain JD, Long NC, Wolfthal SF, Dumyahn T, Dockery DW (1998) Pulmonary toxicity in hamsters of smoke particles from Kuwaiti oil fires. Environ Health Perspect 106(3):141–146PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Pope CA III, Dockery DW, Kanner RE, Villegas GM, Schwartz J (1999a) Oxygen saturation, pulse rate, and particulate air pollution: a daily time-series panel study. Am J Respir Crit Care Med 159(2):365–372. doi: 10.1164/ajrccm.159.2.9702103 CrossRefGoogle Scholar
  75. 75.
    Seaton A, Soutar A, Crawford V, Elton R, McNerlan S, Cherrie J, Watt M, Agius R, Stout R (1999) Particulate air pollution and the blood. Thorax 54(11):1027–1032PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Shukla A, Timblin C, BeruBe K, Gordon T, McKinney W, Driscoll K, Vacek P, Mossman BT (2000) Inhaled particulate matter causes expression of nuclear factor (NF)-kappaB-related genes and oxidant-dependent NF-kappaB activation in vitro. Am J Respir Cell Mol Biol 23(2):182–187. doi: 10.1165/ajrcmb.23.2.4035 PubMedCrossRefGoogle Scholar
  77. 77.
    Hoffmann B, Moebus S, Mohlenkamp S, Stang A, Lehmann N, Dragano N, Schmermund A, Memmesheimer M, Mann K, Erbel R, Jockel KH (2007) Residential exposure to traffic is associated with coronary atherosclerosis. Circulation 116(5):489–496. doi: 10.1161/Circulationaha.107.693622 PubMedCrossRefGoogle Scholar
  78. 78.
    Poloniecki JD, Atkinson RW, deLeon AP, Anderson HR (1997) Daily time series for cardiovascular hospital admissions and previous day’s air pollution in London, UK. Occup Environ Med 54(8):535–540PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Brook RD, Franklin B, Cascio W, Hong YL, Howard G, Lipsett M, Luepker R, Mittleman M, Samet J, Smith SC, Tager I (2004b) Air pollution and cardiovascular disease—a statement for healthcare professionals from the expert panel on population and prevention science of the American Heart Association. Circulation 109(21):2655–2671. doi: 10.1161/01.Cir.0000128587.30041.C8 PubMedCrossRefGoogle Scholar
  80. 80.
    Sun QH, Yue PB, Ying ZK, Cardounel AJ, Brook RD, Devlin R, Hwang JS, Zweier JL, Chen LC, Rajagopalan S (2008) Air pollution exposure potentiates hypertension through reactive oxygen species-mediated activation of Rho/ROCK. Arteriosclerosis Thrombosis and Vascular Biology 28(10):1760–1766. doi: 10.1161/Atvbaha.108.166967 CrossRefGoogle Scholar
  81. 81.
    Kampfrath T, Maiseyeu A, Ying ZK, Shah Z, Deiuliis JA, Xu XH, Kherada N, Brook RD, Reddy KM, Padture NP, Parthasarathy S, Chen LC, Moffatt-Bruce S, Sun QH, Morawietz H, Rajagopalan S (2011) Chronic fine particulate matter exposure induces systemic vascular dysfunction via NADPH oxidase and TLR4 pathways. Circ Res 108(6):716–U400. doi: 10.1161/Circresaha.110.237560 PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Nolan J, Batin PD, Andrews R, Lindsay SJ, Brooksby P, Mullen H, Baig W, Flapan AD, Cowley A, Prescott RJ, Neilson JMM, Fox KAA (1998) Prospective study of heart rate variability and mortality in chronic heart failure—results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-Heart). Circulation 98(15):1510–1516PubMedCrossRefGoogle Scholar
  83. 83.
    Hoek G, Brunekreef B, Fischer P, van Wijnen J (2001) The association between air pollution and heart failure, arrhythmia, embolism, thrombosis, and other cardiovascular causes of death in a time series study. Epidemiology 12(3):355–357. doi: 10.1097/00001648-200105000-00017 PubMedCrossRefGoogle Scholar
  84. 84.
    Camm AJ, Malik M, Bigger JT, Breithardt G, Cerutti S, Cohen RJ, Coumel P, Fallen EL, Kennedy HL, Kleiger RE, Lombardi F, Malliani A, Moss AJ, Rottman JN, Schmidt G, Schwartz PJ, Singer D (1996) Heart rate variability—standards of measurement, physiological interpretation, and clinical use. Circulation 93(5):1043–1065CrossRefGoogle Scholar
  85. 85.
    Pope CA, Verrier RL, Lovett EG, Larson AC, Raizenne ME, Kanner RE, Schwartz J, Villegas M, Gold DR, Dockery DW (1999b) Heart rate variability associated with particulate air pollution. Am Heart J 138(5):890–899. doi: 10.1016/S0002-8703(99)70014-1 PubMedCrossRefGoogle Scholar
  86. 86.
    Magari SR, Hauser R, Schwartz J, Williams PL, Smith TJ, Christiani DC (2001) Association of heart rate variability with occupational and environmental exposure to particulate air pollution. Circulation 104(9):986–991. doi: 10.1161/hc3401.095038 PubMedCrossRefGoogle Scholar
  87. 87.
    Creason J, Neas L, Walsh D, Williams R, Sheldon L, Liao DP, Shy C (2001) Particulate matter and heart rate variability among elderly retirees: the Baltimore 1998 PM study. J Expo Anal Environ Epidemiol 11(2):116–122. doi: 10.1038/sj.jea.7500154 PubMedCrossRefGoogle Scholar
  88. 88.
    Seaton A, Macnee W, Donaldson K, Godden D (1995) Particulate air-pollution and acute health-effects. Lancet 345(8943):176–178. doi: 10.1016/S0140-6736(95)90173-6 PubMedCrossRefGoogle Scholar
  89. 89.
    Ghelfi E, Wellenius GA, Lawrence J, Millet E, Gonzalez-Flecha B (2010) Cardiac oxidative stress and dysfunction by fine concentrated ambient particles (CAPs) are mediated by angiotensin-II. Inhal Toxicol 22(11):963–972. doi: 10.3109/08958378.2010.503322 PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Xia T, Kovochich M, Nel A (2006) The role of reactive oxygen species and oxidative stress in mediating particulate matter injury. Clinics in occupational and environmental medicine 5(4):817–836. doi: 10.1016/j.coem.2006.07.005 PubMedGoogle Scholar
  91. 91.
    Mangge H, Becker K, Fuchs D, Gostner JM (2014) Antioxidants, inflammation and cardiovascular disease. World J Cardiol 6(6):462–477. doi: 10.4330/wjc.v6.i6.462 PubMedPubMedCentralCrossRefGoogle Scholar
  92. 92.
    Cui Y, Xie X, Jia F, He J, Li Z, Fu M, Hao H, Liu Y, Liu JZ, Cowan PJ, Zhu H, Sun Q, Liu Z (2015) Ambient fine particulate matter induces apoptosis of endothelial progenitor cells through reactive oxygen species formation. Cellular physiology and biochemistry: international journal of experimental cellular physiology, biochemistry, and pharmacology 35(1):353–363. doi: 10.1159/000369701 CrossRefGoogle Scholar
  93. 93.
    Gammone MA, Riccioni G, D'Orazio N (2015) Carotenoids: potential allies of cardiovascular health? Food Nutr Res 59:26762. doi: 10.3402/fnr.v59.26762 PubMedCrossRefGoogle Scholar
  94. 94.
    Peter S, Holguin F, Wood LG, Clougherty JE, Raederstorff D, Antal M, Weber P, Eggersdorfer M (2015) Nutritional solutions to reduce risks of negative health impacts of air pollution. Nutrients 7(12):10398–10416. doi: 10.3390/nu7125539 PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Pinho RA, Silveira PC, Silva LA, Luiz Streck E, Dal-Pizzol F,  F Moreira JC (2005) N-acetylcysteine and deferoxamine reduce pulmonary oxidative stress and inflammation in rats after coal dust exposure. Environ Res 99(3):355–360. doi: 10.1016/j.envres.2005.03.005
  96. 96.
    Rhoden CR, Wellenius GA, Ghelfi E, Lawrence J, Gonzalez-Flecha B (2005) PM-induced cardiac oxidative stress and dysfunction are mediated by autonomic stimulation. Biochim Biophys Acta 1725(3):305–313. doi: 10.1016/j.bbagen.2005.05.025 PubMedCrossRefGoogle Scholar
  97. 97.
    Riccioni G, D'Orazio N, Palumbo N, Bucciarelli V, Ilio E, Bazzano LA, Bucciarelli T (2009) Relationship between plasma antioxidant concentrations and carotid intima-media thickness: the Asymptomatic Carotid Atherosclerotic Disease in Manfredonia Study. European journal of cardiovascular prevention and rehabilitation: official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology 16(3):351–357. doi: 10.1097/HJR.0b013e328325d807 CrossRefGoogle Scholar
  98. 98.
    Siems W, Wiswedel I, Salerno C, Crifo C, Augustin W, Schild L, Langhans CD, Sommerburg O (2005) Beta-carotene breakdown products may impair mitochondrial functions—potential side effects of high-dose beta-carotene supplementation. J Nutr Biochem 16(7):385–397. doi: 10.1016/j.jnutbio.2005.01.009 PubMedCrossRefGoogle Scholar
  99. 99.
    Singh U, Devaraj S, Jialal I (2005) Vitamin E, oxidative stress, and inflammation. Annu Rev Nutr 25:151–174. doi: 10.1146/annurev.nutr.24.012003.132446 PubMedCrossRefGoogle Scholar
  100. 100.
    Kris-Etherton PM, Harris WS, Appel LJ, Association AHANCAH (2003) Omega-3 fatty acids and cardiovascular disease: new recommendations from the American Heart Association. Arterioscler Thromb Vasc Biol 23(2):151–152PubMedCrossRefGoogle Scholar
  101. 101.
    Erickson KL, Medina EA, Hubbard NE (2000) Micronutrients and innate immunity. The Journal of infectious diseases 182(Suppl 1):S5–10. doi: 10.1086/315922 PubMedCrossRefGoogle Scholar
  102. 102.
    Omenn GS, Goodman GE, Thornquist MD, Balmes J, Cullen MR, Glass A, Keogh JP, Meyskens FL, Valanis B, Williams JH, Barnhart S, Hammar S (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334(18):1150–1155. doi: 10.1056/NEJM199605023341802 PubMedCrossRefGoogle Scholar
  103. 103.
    Marchioli R, Barzi F, Bomba E, Chieffo C, Di Gregorio D, Di Mascio R, Franzosi MG, Geraci E, Levantesi G, Maggioni AP, Mantini L, Marfisi RM, Mastrogiuseppe G, Mininni N, Nicolosi GL, Santini M, Schweiger C, Tavazzi L, Tognoni G, Tucci C, Valagussa F, Investigators GI-P (2002) Early protection against sudden death by n-3 polyunsaturated fatty acids after myocardial infarction: time-course analysis of the results of the Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI)-Prevenzione. Circulation 105(16):1897–1903PubMedCrossRefGoogle Scholar
  104. 104.
    Romieu I, Tellez-Rojo MM, Lazo M, Manzano-Patino A, Cortez-Lugo M, Julien P, Belanger MC, Hernandez-Avila M, Holguin F (2005) Omega-3 fatty acid prevents heart rate variability reductions associated with particulate matter. Am J Respir Crit Care Med 172(12):1534–1540. doi: 10.1164/rccm.200503-372OC PubMedCrossRefGoogle Scholar
  105. 105.
    Schwartz J, Park SK, O'Neill MS, Vokonas PS, Sparrow D, Weiss S, Kelsey K (2005) Glutathione-S-transferase M1, obesity, statins, and autonomic effects of particles: gene-by-drug-by-environment interaction. Am J Respir Crit Care Med 172(12):1529–1533. doi: 10.1164/rccm.200412-1698OC PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  1. 1.I.O.S, Southern Italy Hospital InstituteMedicina Futura ResearchNaplesItaly
  2. 2.Department of Advanced Biomedical SciencesUniversity Federico II of NaplesNaplesItaly
  3. 3.Division of Cardiac SurgeryAOU San Giovanni di Dio e Ruggi d’AragonaSalernoItaly
  4. 4.Department of Medicine and SurgeryUniversity of SalernoBaronissiItaly

Personalised recommendations