Thromb Haemost 2018; 118(02): 266-278
DOI: 10.1160/TH17-05-0362
Coagulation and Fibrinolysis
Schattauer GmbH Stuttgart

Urban Particulate Matter Induces Changes in Gene Expression in Vascular Endothelial Cells that Are Associated with Altered Clot Structure In Vitro

Xiaoxi Pan
,
Yun Yun Gong
,
Ya Xu
,
Robert A. S. Ariens*
,
Michael N. Routledge*
Further Information

Publication History

25 May 2017

01 November 2017

Publication Date:
29 January 2018 (online)

Abstract

Background Particulate matter contained in ambient air pollution has been associated with cardiovascular diseases in several epidemiological studies.

Objective The aim of this study was to investigate the potential for urban particulate matter to induce changes in clot structure through interaction with vascular endothelial cells.

Methods We examined the structure of clots formed on human umbilical vascular endothelial cells that had been treated with various types of particles versus those formed on untreated cells. Particles used were standard reference particulate matter from diesel engine emissions (SRM2975) and urban ambient collection (SRM2787).

Results There was a dose-dependent increase in fibre density in clots formed on particle-treated endothelial cells. It was also found that exposure to the particles induced increased expression of tissue factor and reduced expression of thrombomodulin genes as measured by real-time polymerase chain reaction and increased expression of von Willebrand factor and plasminogen activation inhibitor-1 as measured by ELISA.

Conclusion These changes are consistent with increased procoagulant activity of air pollution particulate matter–treated endothelial cells and suggest that particulate matter has the potential to promote clot formation through changes induced in endothelial genes controlling clot formation.

* These authors contributed equally.


 
  • References

  • 1 Newby DE, Mannucci PM, Tell GS. , et al; ESC Working Group on Thrombosis, European Association for Cardiovascular Prevention and Rehabilitation; ESC Heart Failure Association. Expert position paper on air pollution and cardiovascular disease. Eur Heart J 2015; 36 (02) 83-93b
  • 2 Franchini M, Mannucci PM. Short-term effects of air pollution on cardiovascular diseases: outcomes and mechanisms. J Thromb Haemost 2007; 5 (11) 2169-2174
  • 3 Langrish JP, Bosson J, Unosson J. , et al. Cardiovascular effects of particulate air pollution exposure: time course and underlying mechanisms. J Intern Med 2012; 272 (03) 224-239
  • 4 Kim K-H, Kabir E, Kabir S. A review on the human health impact of airborne particulate matter. Environ Int 2015; 74: 136-143
  • 5 Mills NL, Donaldson K, Hadoke PW. , et al. Adverse cardiovascular effects of air pollution. Nat Clin Pr Cardiovasc Med 2009; 6: 36-44
  • 6 World Health Organisation. Air quality and health. 2011. Available at: http://www.who.int/mediacentre/factsheets/fs313/en/
  • 7 Polichetti G, Cocco S, Spinali A, Trimarco V, Nunziata A. Effects of particulate matter (PM(10), PM(2.5) and PM(1)) on the cardiovascular system. Toxicology 2009; 261 (1-2): 1-8
  • 8 Sun Q, Hong X, Wold LE. Cardiovascular effects of ambient particulate air pollution exposure. Circulation 2010; 121 (25) 2755-2765
  • 9 Pope III CA. The expanding role of air pollution in cardiovascular disease: does air pollution contribute to risk of deep vein thrombosis?. Circulation 2009; 119 (24) 3050-3052
  • 10 Brook RD. Cardiovascular effects of air pollution. Clin Sci (Lond) 2008; 115 (06) 175-187
  • 11 Shah AS, Langrish JP, Nair H. , et al. Global association of air pollution and heart failure: a systematic review and meta-analysis. Lancet 2013; 382 (9897): 1039-1048
  • 12 Snow SJ, Cheng W, Wolberg AS, Carraway MS. Air pollution upregulates endothelial cell procoagulant activity via ultrafine particle-induced oxidant signaling and tissue factor expression. Toxicol Sci 2014; 140 (01) 83-93
  • 13 Wichmann H-E, Peters A. Epidemiological evidence of the effects of ultrafine particle exposure. Philos Trans R Soc A Math Phys Eng Sci 2000; 358: 2751-2769
  • 14 Nemmar A, Hoet PH, Vanquickenborne B. , et al. Passage of inhaled particles into the blood circulation in humans. Circulation 2002; 105 (04) 411-414
  • 15 Brook RD, Rajagopalan S, Pope III CA. , et al; American Heart Association Council on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, and Council on Nutrition, Physical Activity and Metabolism. Particulate matter air pollution and cardiovascular disease: an update to the scientific statement from the American Heart Association. Circulation 2010; 121 (21) 2331-2378
  • 16 Baccarelli A, Zanobetti A, Martinelli I. , et al. Effects of exposure to air pollution on blood coagulation. J Thromb Haemost 2007; 5 (02) 252-260
  • 17 Altemose B, Robson MG, Kipen HM. , et al. Association of air pollution sources and aldehydes with biomarkers of blood coagulation, pulmonary inflammation, and systemic oxidative stress. J Expo Sci Environ Epidemiol 2007; 27 (03) 244-250
  • 18 Franchini M, Mannucci PM. Air pollution and cardiovascular disease. Thromb Res 2012; 129 (03) 230-234
  • 19 Chuang KJ, Chan CC, Su TC, Lee CT, Tang CS. 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 (04) 370-376
  • 20 Baccarelli A, Martinelli I, Pegoraro V. , et al. Living near major traffic roads and risk of deep vein thrombosis. Circulation 2009; 119 (24) 3118-3124
  • 21 Pan X, Gong YY, Martinelli I. , et al. Fibrin clot structure is affected by levels of particulate air pollution exposure in patients with venous thrombosis. Environ Int 2016; 92-93: 70-76
  • 22 Metassan S, Routledge MN, Lucking AJ. , et al. Fibrin clot structure remains unaffected in young, healthy individuals after transient exposure to diesel exhaust. Part Fibre Toxicol 2010; 7: 17
  • 23 Supino R. MTT assays. Methods Mol Biol 1995; 43: 137-149
  • 24 Metassan S, Charlton AJ, Routledge MN, Scott DJ, Ariëns RA. Alteration of fibrin clot properties by ultrafine particulate matter. Thromb Haemost 2010; 103 (01) 103-113
  • 25 Wu Y, Yu T, Gilbertson TA, Zhou A, Xu H, Nguyen KT. Biophysical assessment of single cell cytotoxicity: diesel exhaust particle-treated human aortic endothelial cells. PLoS One 2012; 7 (05) e36885
  • 26 Okraska-Bylica A, Wilkosz T, Słowik L, Bazanek M, Konieczyńska M, Undas A. Altered fibrin clot properties in patients with premature peripheral artery disease. Pol Arch Med Wewn 2012; 122 (12) 608-615
  • 27 Palka I, Nessler J, Nessler B, Piwowarska W, Tracz W, Undas A. Altered fibrin clot properties in patients with chronic heart failure and sinus rhythm: a novel prothrombotic mechanism. Heart 2010; 96 (14) 1114-1118
  • 28 Undas A, Ariëns RAS. Fibrin clot structure and function: a role in the pathophysiology of arterial and venous thromboembolic diseases. Arterioscler Thromb Vasc Biol 2011; 31 (12) e88-e99
  • 29 Steffel J, Lüscher TF, Tanner FC. Tissue factor in cardiovascular diseases: molecular mechanisms and clinical implications. Circulation 2006; 113 (05) 722-731
  • 30 Karoly ED, Li Z, Dailey LA, Hyseni X, Huang YC. Up-regulation of tissue factor in human pulmonary artery endothelial cells after ultrafine particle exposure. Environ Health Perspect 2007; 115 (04) 535-540
  • 31 Milano M, Dongiovanni P, Artoni A. , et al. Particulate matter phagocytosis induces tissue factor in differentiating macrophages. J Appl Toxicol 2016; 36 (01) 151-160
  • 32 Chu AJ. Tissue factor mediates inflammation. Arch Biochem Biophys 2005; 440 (02) 123-132
  • 33 Tatsumi K, Mackman N. Tissue factor and atherothrombosis. J Atheroscler Thromb 2015; 22 (06) 543-549
  • 34 Belting M, Ahamed J, Ruf W. Signaling of the tissue factor coagulation pathway in angiogenesis and cancer. Arterioscler Thromb Vasc Biol 2005; 25 (08) 1545-1550
  • 35 Versteeg HH, Spek CA, Slofstra SH, Diks SH, Richel DJ, Peppelenbosch MP. FVIIa:TF induces cell survival via G12/G13-dependent Jak/STAT activation and BclXL production. Circ Res 2004; 94 (08) 1032-1040
  • 36 Lenting PJ, Casari C, Christophe OD, Denis CV. von Willebrand factor: the old, the new and the unknown. J Thromb Haemost 2012; 10 (12) 2428-2437
  • 37 Mannucci PM. von Willebrand factor: a marker of endothelial damage?. Arterioscler Thromb Vasc Biol 1998; 18 (09) 1359-1362
  • 38 Vischer UM. von Willebrand factor, endothelial dysfunction, and cardiovascular disease. J Thromb Haemost 2006; 4 (06) 1186-1193
  • 39 Ruggeri ZM. Von Willebrand factor, platelets and endothelial cell interactions. J Thromb Haemost 2003; 1 (07) 1335-1342
  • 40 De Meyer SF, Deckmyn H, Vanhoorelbeke K. von Willebrand factor to the rescue. Blood 2009; 113 (21) 5049-5057
  • 41 Lenting PJ, van Mourik JA, Mertens K. The life cycle of coagulation factor VIII in view of its structure and function. Blood 1998; 92 (11) 3983-3996
  • 42 Koster T, Blann AD, Briët E, Vandenbroucke JP, Rosendaal FR. Role of clotting factor VIII in effect of von Willebrand factor on occurrence of deep-vein thrombosis. Lancet 1995; 345 (8943): 152-155
  • 43 Kohler HP, Grant PJ. Plasminogen-activator inhibitor type 1 and coronary artery disease. N Engl J Med 2000; 342 (24) 1792-1801
  • 44 Su T-C, Chan C-C, Liau C-S, Lin LY, Kao HL, Chuang KJ. Urban air pollution increases plasma fibrinogen and plasminogen activator inhibitor-1 levels in susceptible patients. Eur J Cardiovasc Prev Rehabil 2006; 13 (05) 849-852
  • 45 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; 6 (04) e18525
  • 46 Mills NL, Törnqvist 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 (11) 1075-1082
  • 47 Carter AM. Inflammation, thrombosis and acute coronary syndromes. Diab Vasc Dis Res 2005; 2 (03) 113-121
  • 48 Mills NL, Törnqvist H, Robinson SD. , et al. Air pollution and atherothrombosis. Inhal Toxicol 2007; 19 (19) (Suppl. 01) 81-89
  • 49 Vaughan DE. PAI-1 and atherothrombosis. J Thromb Haemost 2005; 3 (08) 1879-1883
  • 50 Aso Y. Plasminogen activator inhibitor (PAI)-1 in vascular inflammation and thrombosis. Front Biosci 2007; 12: 2957-2966
  • 51 Fuentes-Prior P, Iwanaga Y, Huber R. , et al. Structural basis for the anticoagulant activity of the thrombin-thrombomodulin complex. Nature 2000; 404 (6777): 518-525
  • 52 Li Y-H, Kuo C-H, Shi G-Y. , et al. The role of thrombomodulin lectin-like domain in inflammation. J Biomed Sci 2012; 19: 34
  • 53 Versteeg HH, Heemskerk JW, Levi M, Reitsma PH. New fundamentals in hemostasis. Physiol Rev 2013; 93 (01) 327-358
  • 54 Poursafa P, Kelishadi R, Lahijanzadeh A. , et al. The relationship of air pollution and surrogate markers of endothelial dysfunction in a population-based sample of children. BMC Public Health 2011; 11: 115
  • 55 Lodovici M, Bigagli E. Oxidative stress and air pollution exposure. J Toxicol 2011; 2011: 487074
  • 56 Healey K, Smith EC, Wild CP, Routledge MN. The mutagenicity of urban particulate matter in an enzyme free system is associated with the generation of reactive oxygen species. Mutat Res 2006; 602 (1-2): 1-6