The procoagulant effects of air pollution
2007; Elsevier BV; Volume: 5; Issue: 2 Linguagem: Inglês
10.1111/j.1538-7836.2007.02344.x
ISSN1538-7933
Autores Tópico(s)Energy and Environment Impacts
ResumoThe effects of air pollution on health have become a major concern for politicians and an almost daily topic for newspapers. A Google search using 'air pollution and health' provides over 18 000 000 entries. Air pollution has been linked not only to pulmonary disease, but also to cardiovascular disease. Both acute [1Peters A. Dockery D.W. Muller J.E. Mittleman M.A. Increased particulate air pollution and the triggering of myocardial infarction.Circulation. 2001; 103: 2810-5Crossref PubMed Google Scholar, 2Peters A. Von Klot S. Heier M. Trentinaglia I. Hormann A. Wichmann H.E. Lowel H. Exposure to traffic and the onset of myocardial infarction.N Engl J Med. 2004; 351: 1721-30Crossref PubMed Scopus (769) Google Scholar] and chronic [3Pope III, C.A. Burnett R.T. Thurston G.D. Thun M.J. Calle E.E. Krewski D. Godleski J.J. Cardiovascular mortality and long‐term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease.Circulation. 2004; 109: 71-77Crossref PubMed Scopus (0) Google Scholar] exposure to polluted air are associated with an increased incidence of acute myocardial infarction. Mechanistic explanations for this association are actively being sought [4Vermylen J. Nemmar A. Nemery B. Hoylaerts M.F. Ambient air pollution and acute myocardial infarction.J Thromb Haemost. 2005; 3: 1955-61Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. The current issue of this Journal contains a remarkable piece of detective work that took place in the region of Lombardy, northern Italy. This region contains both the often heavily polluted industrial area around Milan, and idyllic places such as the Como lake and the southern Alpine slopes. The A. Bianchi Bonomi Haemophilia and Thrombosis Centre in Milan collected blood over a period of 10 years from 1218 healthy individuals from this region, who were partners or friends of patients with thrombosis, and who agreed to undergo thrombophilia testing. The very original feature of this study by Baccarelli et al. [5Baccarelli A. Zanobetti A. Martinelli I. Grillo P. Hou L. Giacomini S. Bonzini M. Lanzani G. Mannucci P.M. Bertazzi P.A. Schwartz J. Effects of exposure to air pollution on blood coagulation.J Thromb Haemost. 2007; 5: 252-60Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar] is that it relates the results of the clotting tests to the degree of air pollution, in the hours and days before sampling, in the area where the subject lived. Surprisingly, a weak but significant negative correlation was found between the prothrombin time and the degree of air pollution at the time of sampling or the average air pollution in the 30 days prior to sampling. The degree of air pollution had no effect on the activated partial thromboplastin time or on the levels of fibrinogen, antithrombin, protein C or protein S. In a separate paper on the same healthy subjects, Baccarelli et al. [6Baccarelli A, Zanobetti A, Martinelli I, Grillo P, Hou L, Lanzani G, Mannucci PM, Bertazzi PA, Schwartz J. Air pollution, smoking and plasma homocysteine. Environ Health Perspect; DOI: 10.1289/ehp.9517.Google Scholar] report that particulate air pollution interacts with cigarette smoking to increase plasma homocysteine levels. Until now, relatively little attention has been paid to slight shortenings of the prothrombin time, a very frequently performed global coagulation test. Infusion of recombinant factor VIIa, however, results in a markedly shortened prothrombin time [7Lindley C.M. Sawyer W.T. Macik B.G. Lusher J. Harrison J.F. Baird‐Cox K. Birch K. Glazer S. Roberts H.R. Pharmacokinetics and pharmacodynamics of recombinant factor VIIa.Clin Pharmacol Ther. 1994; 55: 638-48Crossref PubMed Google Scholar]. As Baccarelli et al. [5Baccarelli A. Zanobetti A. Martinelli I. Grillo P. Hou L. Giacomini S. Bonzini M. Lanzani G. Mannucci P.M. Bertazzi P.A. Schwartz J. Effects of exposure to air pollution on blood coagulation.J Thromb Haemost. 2007; 5: 252-60Abstract Full Text Full Text PDF PubMed Scopus (179) Google Scholar] suggest, the somewhat shortened prothrombin time following exposure to polluted air could well result from an increased FVIIa level, in view of the absence of any shortening of the activated partial thromboplastin time. Measurement of FVIIa was, however, not included in the screening of these healthy individuals. An increase in FVIIa levels may reflect exposure of the blood to tissue factor. What could be the link between air pollution and tissue factor? Associations have already been found between smoking and circulating tissue factor activity [8Sambola A. Osende J. Hathcock J. Degen M. Nemerson Y. Fuster V. Crandall J. Badimon J.J. Role of risk factors in the modulation of tissue factor activity and blood thrombogenicity.Circulation. 2003; 107: 973-7Crossref PubMed Scopus (258) Google Scholar] and FVIIa levels [9Danielsen R. Onundarson P.T. Thors H. Vidarsson B. Morrissey J.H. Activated and total coagulation factor VII, and fibrinogen in coronary artery disease.Scand Cardiovasc J. 1998; 32: 87-95Crossref PubMed Scopus (0) Google Scholar]. Exposure to polluted air causes pulmonary inflammation in humans, as evidenced by the presence of inflammatory cells in sputum [10Nightingale J.A. Maggs R. Cullinan P. Donnelly L.E. Rogers D.F. Kinnersley R. Chung K.F. Barnes P.J. Ashmore M. Newman‐Taylor A. Airway inflammation after controlled exposure to diesel exhaust particles.Am J Respir Crit Care Med. 2000; 162: 161-6Crossref PubMed Google Scholar] and in bronchoalveolar lavage fluid [11Ghio A.J. Kim C. Devlin R.B. Concentrated ambient air particles induce mild pulmonary inflammation in healthy human volunteers.Am J Respir Crit Care Med. 2000; 162: 981-8Crossref PubMed Google Scholar]. Following intratracheal instillation of diesel exhaust particles in hamsters, there is a strict link between the degree of lung inflammation and the extent of thrombosis following minor vascular injury [12Nemmar A. Nemery B. Hoet P.H. Vermylen J. Hoylaerts M.F. Pulmonary inflammation and thrombogenicity caused by diesel particles in hamsters: role of histamine.Am J Respir Crit Care Med. 2003; 168: 1366-72Crossref PubMed Scopus (0) Google Scholar]. Inflamed pulmonary endothelial cells would expose adhesion molecules, including P‐selectin and von Willebrand factor [13Wagner J.G. Roth R.A. Neutrophil migration mechanisms, with an emphasis on the pulmonary vasculature.Pharmacol Rev. 2000; 52: 349-74PubMed Google Scholar], resulting in binding and mutual activation of leukocytes and platelets, which could then lead to the release of leukocyte‐derived tissue factor‐containing microparticles into the circulation [14Hrachovinova I. Cambien B. Hafezi‐Moghadam A. Kappelmayer J. Camphuisen R.T. Widom A. Xia L. Kazazian Jr, H.H. Schaub R.G. McEver R.P. Wagner D.D. Interaction of P‐selectin and PSGL‐1 generates microparticles that correct hemostasis in a mouse model of hemophilia A.Nat Med. 2003; 9: 1020-5Crossref PubMed Scopus (0) Google Scholar]. Alternatively, pulmonary inflammation because of air pollution is known to be associated with release of proinflammatory cytokines into the circulation, namely interleukin‐1β, interleukin‐6 and granulocyte–macrophage colony‐stimulating factor [15Van Eeden S.F. Tan W.C. Sawa I. Mukae H. Terashima T. Fujii T. Qui D. Vincent R. Hogg J.C. Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)).Am J Respir Crit Care Med. 2001; 164: 826-30Crossref PubMed Google Scholar]. Exposure to polluted air further stimulates the release of neutrophils [16Salvi S. Blomberg A. Rudell B. Kelly F. Sandström T. Holgate S.T. Frew A. Acute inflammatory responses in the airways and peripheral blood after short‐term exposure to diesel exhaust in healthy human volunteers.Am J Respir Crit Care Med. 1999; 159: 702-9Crossref PubMed Google Scholar, 17Tan W.C. Qiu D. Liam B.L. Ng T.P. Lee S.H. Van Eeden S.F. D'Yachkova Y. Hogg J.C. The human bone marrow response to acute air pollution caused by forest fires.Am J Respir Crit Care Med. 2000; 161: 1213-7Crossref PubMed Google Scholar] and monocytes [18Goto Y. Ishii H. Hogg J.C. Shih C.H. Yatera K. Vincent R. Van Eeden S.F. Particulate air matter stimulates monocyte release from the bone marrow..Am J Respir Crit Care Med. 2004; 170: 891-7Crossref PubMed Scopus (0) Google Scholar] from the bone marrow. One could assume that inhalation of pollutants may also release hematopoietic cell‐derived microparticles carrying tissue factor [19Chou J. Mackman N. Merrill‐Skoloff G. Pedersen B. Furie B.C. Furie B. Hematopoietic cell‐derived microparticle tissue factor contributes to fibrin formation during thrombus propagation.Blood. 2004; 104: 3190-7Crossref PubMed Scopus (0) Google Scholar] from the bone marrow into the circulation. Tissue factor‐bearing microparticles derived from leukocytes deposit on a layer of activated platelets [20Giesen P.L. Rauch U. Bohrmann B. Kling D. Roque M. Fallon J.T. Badimon J.J. Himber J. Riederer M.A. Nemerson Y. Blood‐borne tissue factor: another view of thrombosis.Proc Natl Acad Sci USA. 1999; 96: 2311-5Crossref PubMed Scopus (0) Google Scholar, 21Falati S. Liu Q. Gross P. 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A new animal model of thrombophilia confirms that high plasma factor VIII levels are thrombogenic.Thromb Haemost. 1999; 81: 306-11Crossref PubMed Google Scholar, 25Hoffman M. Monroe D.M. Roberts H.R. Coagulation factor IXa binding to activated platelets and platelet‐derived microparticles: a flow cytometric study.Thromb Haemost. 1992; 68: 74-8Crossref PubMed Scopus (0) Google Scholar, 26Baglia F.A. Shrimpton C.N. Emsley J. Kitawaga K. Ruggeri Z.M. Lopez J.A. Walsh P.N. Factor XI interacts with the leucine‐rich repeats of glycoprotein Ib alpha on the activated platelet.J Biol Chem. 2004; 279: 49323-9Abstract Full Text Full Text PDF PubMed Scopus (0) Google Scholar]. The interaction of tissue factor with clotting factors concentrated on a platelet layer overlying a vascular lesion would result in a local burst of thrombin activity that could readily lead to an occlusive thrombosis. It thus becomes understandable how exposure to polluted air may trigger within hours a myocardial infarction in a susceptible individual [27Goldberg M.S. Burnett R.T. Bailar III, J.C. Tamblyn R. Ernst P. Flegel K. Brook J. Bonvalot Y. Singh R. Valois M.F. Vincent R. Identification of persons with cardiorespiratory conditions who are at risk of dying from the acute effects of ambient air particles.Environ Health Perspect. 2001; 109: 487-94Crossref Scopus (157) Google Scholar, 28Zanobetti A. Schwartz J. Cardiovascular damage by airborne particles: are diabetics more susceptible.Epidemiology. 2002; 13: 588-92Crossref PubMed Google Scholar, 29Pope C.A. .3.r.d. Muhlestein J.B. May H.T. Renlund D.G. Anderson J.L. Horne B.D. Ischemic heart disease events triggered by short‐term exposure to fine particulate air pollution.Circulation. 2006; 114: 2443-8Crossref PubMed Scopus (0) Google Scholar]. But enough speculation! The time has come to verify whether circulating tissue factor activity and FVIIa level do indeed rise in humans following acute exposure to polluted air, and whether this is related to the gaseous or the particulate matter in the inhaled air, and to the extent of the resulting inflammation. The authors state that they have no conflict of interest.
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