Hamostaseologie 2012; 32(01): 5-13
DOI: 10.5482/ha-1179
Review
Schattauer GmbH

The effect of air pollution on haemostasis

Die Wirkung der Luftverschmutzung auf die Hämostase
J. Emmerechts
1   Center for Molecular and Vascular Biology, University of Leuven, Belgium
,
M. F. Hoylaerts
1   Center for Molecular and Vascular Biology, University of Leuven, Belgium
› Author Affiliations
The CMVB is supported by the “Programmafinanciering KULeuven” (PF/10/014). JE is holder of a grant from the Institute for the Promotion of Innovation through Science and Technology in Flanders (IWTVlaanderen, project 81045).
Further Information

Publication History

received: 03 October 2011

accepted: 06 October 2011

Publication Date:
28 December 2017 (online)

Summary

Ambient environmental air pollutants include gaseous and particulate components. In polluted air, especially particulate matter seems responsible for cardiovascular complications: It consists of a heterogeneous mixture of solid and liquid particles with different diameters ranging from large thoracic to ultrafine particles, with a diameter < 100 nm. Ultrafines can penetrate deeply into the lung to deposit in the alveoli. Cardiovascular manifestations result both from short-term and long-term exposure and have been linked to interference with the autonomic nervous system, direct translocation into the systemic circulation, pulmonary inflammation and oxidative stress. Thrombotic complications associated with air pollution comprise arterial and probably venous thrombogenicity.

This review describes the existing epidemiological and experimental evidence to explain the rapid induction of myocardial infarction within 1–2 hours after exposure to polluted air and advances several explanations as to why more chronic exposure will lead to enhanced venous thrombogenicity. Mechanisms such as platelet activation, endothelial dysfunction, coagulation factor changes and microvesicle production are discussed.

Zusammenfassung

Luftschadstoffe in der Umwelt enthalten gasförmige und korpuskulare Bestandteile. Für kardiovaskuläre Komplikationen scheint besonders der Feinstaub in der schadstoffbelasteten Luft verantwortlich zu sein: Er enthält eine heterogene Mischung aus festen und flüssigen Bestandteilen, deren Durchmesser im Bereich zwischen großen thorakalen bis hin zu ultrafeinen Partikeln (Durchmesser < 100 nm) liegt. Ultrafeine Partikel können tief in die Lunge eindringen und sich in den Alveolen ablagern. Sowohl die kurzfristige als auch die Langzeitexposition führen zu kardiovaskulären Krankheitsbildern, die auf Störungen des autonomen Nervensystems, die direkte Translokation in den systemischen Kreislauf, entzündliche Lungenveränderungen sowie auf oxidativen Stress zurückgeführt wurden. Zu den feinstaubabhängigen thrombotischen Komplikationen gehören arterielle und wahrscheinlich auch venöse prothrombotische Effekte.

In dieser Übersicht werden die epidemiologische und experimentelle Daten dargestellt, welche die rasche Auslösung eines Myokardinfarkts innerhalb von 1–2 Stunden nach Exposition gegenüber verschmutzter Luft erklären. Verschiedene Erklärungsmodelle werden vorgestellt, weshalb die eher chronische Exposition die venöse Thrombogenität erhöht. Mechanismen wie Thrombozytenaktivierung, endotheliale Dysfunktion, Veränderungen der Gerinnungsfaktoren und Produktion von Mikrovesikeln werden diskutiert.

 
  • References

  • 1 Dominici F, Peng RD, Bell ML. et al. Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA 2006; 295: 1127-1134.
  • 2 Maitre A, Bonneterre V, Huillard L. et al. Impact of urban atmospheric pollution on coronary disease. Eur Heart J 2006; 27: 2275-2284.
  • 3 Pope 3rd CA, Burnett RT, Thun MJ. et al. Lung cancer, cardiopulmonary mortality, and long-term exposure to fine particulate air pollution. JAMA 2002; 287: 1132-1141.
  • 4 Simkhovich BZ, Kleinman MT, Kloner RA. Air pollution and cardiovascular injury epidemiology, toxicology, and mechanisms. J Am Coll Cardiol 2008; 52: 719-726.
  • 5 Brook RD, Franklin B, Cascio W. et al. Air pollution and cardiovascular disease. Circulation 2004; 109: 2655-2671.
  • 6 Nemmar A, Nemery B, Hoet PH. et al. Pulmonary inflammation and thrombogenicity caused by diesel particles in hamsters. Am J Respir Crit Care Med 2003; 168: 1366-1372.
  • 7 Nemmar A, Hoet PH, Vandervoort P. et al. Enhanced peripheral thrombogenicity after lung inflammation is mediated by platelet-leukocyte activation. J Thromb Haemost 2007; 05: 1217-1226.
  • 8 Araujo JA, Barajas B, Kleinman M. et al. Ambient particulate pollutants in the ultrafine range promote early atherosclerosis and systemic oxidative stress. Circ Res 2008; 102: 589-596.
  • 9 Pope 3rd CA, Burnett RT, Thurston GD. et al. Cardiovascular mortality and long-term exposure to particulate air pollution. Circulation 2004; 109: 71-77.
  • 10 Baccarelli A, Martinelli I, Zanobetti A. et al. Exposure to particulate air pollution and risk of deep vein thrombosis. Arch Intern Med 2008; 168: 920-927.
  • 11 Dales RE, Cakmak S, Vidal CB. Air pollution and hospitalization for venous thromboembolic disease in Chile. J Thromb Haemost 2010; 08: 669-674.
  • 12 Brook RD, Rajagopalan S, Pope CA. et al. Particulate matter air pollution and cardiovascular disease. Circulation 2010; 121: 2331-2378.
  • 13 Nemmar A, Hoet PH, Vanquickenborne B. et al. Passage of inhaled particles into the blood circulation in humans. Circulation 2002; 105: 411-414.
  • 14 Pery AR, Brochot C, Hoet PH. et al. Development of a physiologically based kinetic model for 99m-technetium-labelled carbon nanoparticles inhaled by humans. Inhal Toxicol 2009; 21: 1099-1107.
  • 15 Araujo JA, Nel AE. Particulate matter and atherosclerosis: role of particle size, composition and oxidative stress. Part Fibre Toxicol 2009; 06: 24.
  • 16 Tao F, Gonzalez-Flecha B, Kobzik L. Reactive oxygen species in pulmonary inflammation by ambient particulates. Free Radic Biol Med 2003; 35: 327-340.
  • 17 Prandoni P. Venous and arterial thrombosis: Two aspects of the same disease?. Clin Epidemiol 2009; 01: 1-6.
  • 18 Dominici F, McDermott A, Daniels M. et al. Mortality among residents of 90 cities. In: Revised Analyses of Time-Series Studies of Air Pollution and Health. Boston, MA: Health Effects Institute; 2003: 9-24.
  • 19 Katsouyanni K, Touloumi G, Samoli E. et al. Confounding and effect modification in the short-term effects of ambient particles on total mortality. Epidemiology 2001; 12: 521-531.
  • 20 Zanobetti A, Schwartz J, Samoli E. et al. The temporal pattern of respiratory and heart disease mortality in response to air pollution. Environ Health Perspect 2003; 111: 1188-1193.
  • 21 Samoli E, Peng R, Ramsay T. et al. Acute effects of ambient particulate matter on mortality in Europe and North America. Environ Health Perspect 2008; 116: 1480-1486.
  • 22 Dockery DW, Pope 3rd CA, Xu X. et al. An association between air pollution and mortality in six US cities. N Engl J Med 1993; 329: 1753-1759.
  • 23 Beelen R, Hoek G, van den Brandt PA. et al. Longterm effects of traffic-related air pollution on mortality in a Dutch cohort (NLCS-AIR study). Environ Health Perspect 2008; 116: 196-202.
  • 24 Laden F, Schwartz J, Speizer FE, Dockery DW. Reduction in fine particulate air pollution and mortality. Am J Respir Crit Care Med 2006; 173: 667-672.
  • 25 Boldo E, Linares C, Lumbreras J. et al. Health impact assessment of a reduction in ambient PM(2.5) levels in Spain. Environ Int 2011; 37: 342-348.
  • 26 Schwartz J, Coull B, Laden F, Ryan L. The effect of dose and timing of dose on the association between airborne particles and survival. Environ Health Perspect 2008; 116: 64-69.
  • 27 Puett RC, Hart JE, Yanosky JD. et al. Chronic fine and coarse particulate exposure, mortality, and coronary heart disease in the Nurses’ Health Study. Environ Health Perspect 2009; 117: 1697-1701.
  • 28 Peters A, Dockery DW, Muller JE, Mittleman MA. Increased particulate air pollution and the triggering of myocardial infarction. Circulation 2001; 103: 2810-2815.
  • 29 Peters A, von Klot S, Heier M. et al. Exposure to traffic and the onset of myocardial infarction. N Engl J Med 2004; 351: 1721-1730.
  • 30 Nawrot TS, Perez L, Kunzli N. et al. Public health importance of triggers of myocardial infarction. Lancet 2011; 377: 732-740.
  • 31 Kunzli N, Jerrett M, Mack WJ. et al. Ambient air pollution and atherosclerosis in Los Angeles. Environ Health Perspect 2005; 113: 201-206.
  • 32 Diez AVRoux, Auchincloss AH, Franklin TG. et al. Long-term exposure to ambient particulate matter and prevalence of subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol 2008; 167: 667-675.
  • 33 Hoffmann B, Moebus S, Mohlenkamp S. et al. Residential exposure to traffic is associated with coronary atherosclerosis. Circulation 2007; 116: 489-496.
  • 34 Kunzli N, Jerrett M, Garcia-Esteban R. et al. Ambient air pollution and the progression of atherosclerosis in adults. PLoS One 2010; 05: e9096.
  • 35 Baccarelli A, Martinelli I, Pegoraro V. et al. Living near major traffic roads and risk of deep vein thrombosis. Circulation 2009; 119: 3118-3124.
  • 36 Shih RA, Griffin BA, Salkowski N. et al. Ambient particulate matter air pollution and venous thromboembolism in the women’s health initiative hormone therapy trials. Environ Health Perspect 2010; 119: 326-331.
  • 37 Kan H, Folsom AR, Cushman M. et al. Traffic exposure and incident venous thromboembolism in the atherosclerosis risk in communities (ARIC) study. J Thromb Haemost 2011; 09: 672-678.
  • 38 Ross R. Atherosclerosis – an inflammatory disease. N Engl J Med 1999; 340: 115-126.
  • 39 Braunwald E. Shattuck lecture – cardiovascular medicine at the turn of the millennium. N Engl J Med 1997; 337: 1360-1369.
  • 40 Stocker R, Keaney Jr JF. Role of oxidative modifications in atherosclerosis. Physiol Rev 2004; 84: 1381-1478.
  • 41 Jimenez LA, Thompson J, Brown DA. et al. Activation of NF-kappaB by PM(10) occurs via an ironmediated mechanism in the absence of IkappaB degradation. Toxicol Appl Pharmacol 2000; 166: 101-110.
  • 42 Carter JD, Ghio AJ, Samet JM, Devlin RB. Cytokine production by human airway epithelial cells after exposure to an air pollution particle is metal-dependent. Toxicol Appl Pharmacol 1997; 146: 180-188.
  • 43 Costa DL, Dreher KL. Bioavailable transition metals in particulate matter mediate cardiopulmonary injury in healthy and compromised animal models. Environ Health Perspect 1997; 105 (Suppl. 05) 1053-1060.
  • 44 Kadiiska MB, Mason RP, Dreher KL. et al. In vivo evidence of free radical formation in the rat lung after exposure to an emission source air pollution particle. Chem Res Toxicol 1997; 10: 1104-1108.
  • 45 Jacobs L, Emmerechts J, Hoylaerts MF. et al. Traffic air pollution and oxidized LDL. PLoS One. 2011 06. 01
  • 46 Suwa T, Hogg JC, Quinlan KB. et al. Particulate air pollution induces progression of atherosclerosis. J Am Coll Cardiol 2002; 39: 935-942.
  • 47 Sun Q, Wang A, Jin X. et al. Long-term air pollution exposure and acceleration of atherosclerosis and vascular inflammation in an animal model. JAMA 2005; 294: 3003-3010.
  • 48 Li N, Alam J, Venkatesan MI. et al. Nrf2 is a key transcription factor that regulates antioxidant defense in macrophages and epithelial cells. J Immunol 2004; 173: 3467-3481.
  • 49 Oberdorster G, Oberdorster E, Oberdorster J. Nanotoxicology: an emerging discipline evolving from studies of ultrafine particles. Environ Health Perspect 2005; 113: 823-839.
  • 50 Theilmeier G, Michiels C, Spaepen E. et al. Endothelial von Willebrand factor recruits platelets to atherosclerosis-prone sites in response to hypercholesterolemia. Blood 2002; 99: 4486-4493.
  • 51 Jacobs L, Emmerechts J, Mathieu C. et al. Air pollution related prothrombotic changes in persons with diabetes. Environ Health Perspect 2009; 118: 191-196.
  • 52 Lucking AJ, Lundback M, Mills NL. et al. Diesel exhaust inhalation increases thrombus formation in man. Eur Heart J 2008; 29: 3043-3051.
  • 53 Rudez G, Janssen NA, Kilinc E. et al. Effects of ambient air pollution on hemostasis and inflammation. Environ Health Perspect 2009; 117: 995-1001.
  • 54 Ruckerl R, Phipps RP, Schneider A. et al. Ultrafine particles and platelet activation in patients with coronary heart disease. Part Fibre Toxicol 2007; 04: 1.
  • 55 Nemmar A, Hoet PH, Dinsdale D. et al. Diesel exhaust particles in lung acutely enhance experimental peripheral thrombosis. Circulation 2003; 107: 1202-1208.
  • 56 Nemmar A, Hoet PH, Vermylen J. et al. Pharmacological stabilization of mast cells abrogates late thrombotic events induced by diesel exhaust particles in hamsters. Circulation 2004; 110: 1670-1677.
  • 57 Nemmar A, Nemery B, Hoet PH. et al. Silica particles enhance peripheral thrombosis: key role of lung macrophage-neutrophil cross-talk. Am J Respir Crit Care Med 2005; 171: 872-879.
  • 58 Nemmar A, Hoylaerts MF, Hoet PH. et al. Size effect of intratracheally instilled particles on pulmonary inflammation and vascular thrombosis. Toxicol Appl Pharmacol 2003; 186: 38-45.
  • 59 Nemmar A, Al-Salam S, Zia S. et al. Time-course effects of systemically administered diesel exhaust particles in rats. Toxicol Lett 2010; 194: 58-65.
  • 60 Yokoyama S, Ikeda H, Haramaki N. et al. Platelet P-selectin plays an important role in arterial thrombogenesis by forming large stable platelet-leukocyte aggregates. J Am Coll Cardiol 2005; 45: 1280-1286.
  • 61 Ray MR, Mukherjee S, Roychoudhury S. et al. Platelet activation, upregulation of CD11b/CD18 expression on leukocytes and increase in circulating leukocyte-platelet aggregates in Indian women chronically exposed to biomass smoke. Hum Exp Toxicol 2006; 25: 627-635.
  • 62 Delfino RJ, Staimer N, Tjoa T. et al. Air pollution exposures and circulating biomarkers of effect in a susceptible population. Environ Health Perspect 2009; 117: 1232-1238.
  • 63 Baccarelli A, Zanobetti A, Martinelli I. et al. Effects of exposure to air pollution on blood coagulation. J Thromb Haemost 2007; 05: 252-260.
  • 64 Bonzini M, Tripodi A, Artoni A. et al. Effects of inhalable particulate matter on blood coagulation. J Thromb Haemost 2010; 08: 662-668.
  • 65 Barregard L, Sallsten G, Gustafson P. et al. Experimental exposure to wood-smoke particles in healthy humans: effects on markers of inflammation, coagulation, and lipid peroxidation. Inhal Toxicol 2006; 18: 845-853.
  • 66 Samet JM, Rappold A, Graff D. et al. Concentrated ambient ultrafine particle exposure induces cardiac changes in young healthy volunteers. Am J Respir Crit Care Med 2009; 179: 1034-1042.
  • 67 Riediker M, Cascio WE, Griggs TR. et al. Particulate matter exposure in cars is associated with cardiovascular effects in healthy young men. Am J Respir Crit Care Med 2004; 169: 934-940.
  • 68 Ruckerl R, Ibald-Mulli A, Koenig W. et al. Air pollution and markers of inflammation and coagulation in patients with coronary heart disease. Am J Respir Crit Care Med 2006; 173: 432-441.
  • 69 Beckett WS, Chalupa DF, Pauly-Brown A. et al. Comparing inhaled ultrafine versus fine zinc oxide particles in healthy adults: a human inhalation study. Am J Respir Crit Care Med 2005; 171: 1129-1135.
  • 70 Brauner EV, Forchhammer L, Moller P. et al. Indoor particles affect vascular function in the aged: an air filtration-based intervention study. Am J Respir Crit Care Med 2008; 177: 419-425.
  • 71 Stewart JC, Chalupa DC, Devlin RB. et al. Vascular effects of ultrafine particles in persons with type 2 diabetes. Environ Health Perspect 2010; 118: 1692-1698.
  • 72 Scharrer E, Hessel H, Kronseder A. et al. Heart rate variability, hemostatic and acute inflammatory blood parameters in healthy adults after short-term exposure to welding fume. Int Arch Occup Environ Health 2007; 80: 265-272.
  • 73 Ghio AJ, Hall A, Bassett MA. et al. Exposure to concentrated ambient air particles alters hematologic indices in humans. Inhal Toxicol 2003; 15: 1465-1478.
  • 74 Blomberg A, Tornqvist H, Desmyter L. et al. Exposure to diesel exhaust nanoparticles does not induce blood hypercoagulability in an at-risk population. J Thromb Haemost 2005; 03: 2103-2105.
  • 75 Carlsten C, Kaufman JD, Peretz A. et al. Coagulation markers in healthy human subjects exposed to diesel exhaust. Thromb Res 2007; 120: 849-855.
  • 76 Ghio AJ, Kim C, Devlin RB. Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers. Am J Respir Crit Care Med 2000; 162: 981-988.
  • 77 Pekkanen J, Brunner EJ, Anderson HR. et al. Daily concentrations of air pollution and plasma fibrinogen in London. Occup Environ Med 2000; 57: 818-822.
  • 78 Chuang KJ, Chan CC, Su TC. et al. The effect of urban air pollution on inflammation, oxidative stress, coagulation, and autonomic dysfunction in young adults. Am J Respir Crit Care Med 2007; 176: 370-376.
  • 79 Thompson AM, Zanobetti A, Silverman F. et al. Baseline repeated measures from controlled human exposure studies: associations between ambient air pollution exposure and the systemic inflammatory biomarkers IL-6 and fibrinogen. Environ Health Perspect 2010; 118: 120-124.
  • 80 Mutlu GM, Green D, Bellmeyer A. et al. Ambient particulate matter accelerates coagulation via an IL- 6-dependent pathway. J Clin Invest 2007; 117: 2952-2961.
  • 81 Budinger GR, McKell JL, Urich D. et al. Particulate matter-induced lung inflammation increases systemic levels of PAI-1 and activates coagulation through distinct mechanisms. PLoS One 2011; 06: e18525.
  • 82 Cozzi E, Wingard CJ, Cascio WE. et al. Effect of ambient particulate matter exposure on hemostasis. Transl Res 2007; 149: 324-332.
  • 83 Inoue K, Takano H, Sakurai M. et al. Pulmonary exposure to diesel exhaust particles enhances coagulatory disturbance with endothelial damage and systemic inflammation related to lung inflammation. Exp Biol Med (Maywood) 2006; 231: 1626-1632.
  • 84 Nadziejko C, Fang K, Chen LC. et al. Effect of concentrated ambient particulate matter on blood coagulation parameters in rats. Res Rep Health Eff Inst 2002; 111: 7-29.
  • 85 Emmerechts J, Alfaro-Moreno E, Vanaudenaerde BM. et al. Short-term exposure to particulate matter induces arterial but not venous thrombosis in healthy mice. J Thromb Haemost 2010; 08: 2651-2661.
  • 86 Kilinc E, Van Oerle R, Borissoff JI. et al. Factor XII activation is essential to sustain the procoagulant effects of particulate matter. J Thromb Haemost 2011; 09: 1359-1367.
  • 87 Morel O, Toti F, Hugel B. et al. Procoagulant microparticles: disrupting the vascular homeostasis equation?. Arterioscler Thromb Vasc Biol 2006; 26: 2594-2604.
  • 88 McVey JH. O tissue factor, where art thou?. Blood 2010; 116: 676-677.
  • 89 Polgar J, Matuskova J, Wagner DD. The P-selectin, tissue factor, coagulation triad. J Thromb Haemost 2005; 03: 1590-1596.
  • 90 Chirinos JA, Heresi GA, Velasquez H. et al. Elevation of endothelial microparticles, platelets, and leukocyte activation in patients with venous thromboembolism. J Am Coll Cardiol 2005; 45: 1467-1471.
  • 91 Bucciarelli P, Martinelli I, Artoni A. et al. Circulating microparticles and risk of venous thromboembolism. Thromb Res. 2011 doi:10.1016/j.thromres.2011.08.020
  • 92 Wilson DW, Aung HH, Lame MW. et al. Exposure of mice to concentrated ambient particulate matter results in platelet and systemic cytokine activation. Inhal Toxicol 2010; 22: 267-276.
  • 93 Mills NL, Tornqvist H, Robinson SD. et al. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation 2005; 112: 3930-3936.
  • 94 Mills NL, Tornqvist H, Gonzalez MC. et al. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med 2007; 357: 1075-1082.
  • 95 Tornqvist H, Mills NL, Gonzalez M. et al. Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am J Respir Crit Care Med 2007; 176: 395-400.
  • 96 O’Toole TE, Hellmann J, Wheat L. et al. Episodic exposure to fine particulate air pollution decreases circulating levels of endothelial progenitor cells. Circ Res 2010; 107: 200-203.
  • 97 Alfaro-Moreno E, Nawrot TS, Vanaudenaerde BM. et al. Co-cultures of multiple cell types mimic pulmonary cell communication in response to urban PM10. Eur Respir J 2008; 32: 1184-1194.
  • 98 Frenette PS, Johnson RC, Hynes RO, Wagner DD. Platelets roll on stimulated endothelium in vivo: an interaction mediated by endothelial P-selectin. Proc Natl Acad Sci USA 1995; 92: 7450-7454.
  • 99 Andre P, Denis CV, Ware J. et al. Platelets adhere to and translocate on von Willebrand factor presented by endothelium in stimulated veins. Blood 2000; 96: 3322-3328.