Pro-thrombotic effect of exercise in a polluted environment: a P-selectin- and CD63-related platelet activation effect

Aurélien Wauters; Fatemeh Esmaeilzadeh; Sandrine Bladt; Ingrid Beukinga; Walter Wijns; Philippe van de Borne; Olivier Pradier; Jean-François Argacha

doi:10.1160/TH14-03-0251

Thrombosis and Haemostasis, Inhaltsverzeichnis

Thromb Haemost 2015; 113(01): 118-124
DOI: 10.1160/TH14-03-0251

Cellular Haemostasis and Platelets

Schattauer GmbH

Pro-thrombotic effect of exercise in a polluted environment: a P-selectin- and CD63-related platelet activation effect

Authors

Aurélien Wauters

¹Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium
Fatemeh Esmaeilzadeh

¹Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium
Sandrine Bladt

²Laboratory of Environmental Research, Institut Bruxellois de Gestion de l’Environnement (IBGE), Belgium
Ingrid Beukinga

³Laboratory of Hematology, Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium
Walter Wijns

³Laboratory of Hematology, Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium
Philippe van de Borne

¹Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium
Olivier Pradier

³Laboratory of Hematology, Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium
Jean-François Argacha

¹Department of Cardiology, Erasme Hospital, Université Libre de Bruxelles (ULB), Belgium

Abstract

Summary

Exposure to diesel exhaust is an important cardiovascular risk factor and may promote atherothrombotic events. Some data suggest that polluted air exposure could affect haemostasis through platelet activation. The aim of the study was to investigate the effects of acute exposure to diesel exhaust on platelet activation and platelet function. We tested the hypothesis in a randomised, crossover study in 25 healthy men exposed to ambient and polluted air; 11 of the subjects also performed exercise during exposure sessions. Platelet activation was evaluated by surface expression of CD62P (P-selectin) and CD63 (dense granule glycoprotein) using flow cytometry of labelled platelets. Platelet function was measured using the PFA-100 platelet function analyser and by Multiplate whole blood impedance platelet aggregometry. Acute diesel exhaust exposure had no effect on platelet activation at rest, but exercise in polluted air increased the collagen- induced expression of CD62P and CD63 (both p< 0.05). The increase in the expression of CD62P and CD63 was related to the total amount of PM2.5 inhaled during the exercise sessions (r=+0.58 and +0.60, respectively, both p< 0.05). Platelet aggregation was not impaired after polluted air exposure at rest or during exercise. In conclusion, in healthy subjects, diesel exhaust exposure induces platelet activation as illustrated by a dose-response increase in the release of CD62P and CD63. This platelet priming effect could be a contributor to the triggering of atherothrombotic events related to air pollution exposure.

Keywords

Environmental (risk) factors - atherothrombosis - platelet glycoproteins

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Referenzen

References
1 Lim SS, Vos T, Flaxman AD. et al. A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380: 2224-2260.
2 Dockery DW, Pope CA, Xu X. et al. An association between air pollution and mortality in six U. S. cities. N Engl J Med 1993; 329: 1753-1759.
3 Laden F, Schwartz J, Speizer FE. et al. Reduction in fine particulate air pollution and mortality: Extended follow-up of the Harvard Six Cities study. Am J Respir Crit Care Med 2006; 173: 667-672.
4 Pope CA, Muhlestein JB, May HT. et al. Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution. Circulation 2006; 114: 2443-2448.
5 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.
6 Nawrot TS, Perez L, Künzli N. et al. Public health importance of triggers of myo-cardial infarction: a comparative risk assessment. Lancet 2011; 377: 732-740.
7 Brook RD, Rajagopalan S, Pope CA. et al. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 2010; 121: 2331-2378.
8 Wauters A, Dreyfuss C, Pochet S. et al. Acute Exposure to Diesel Exhaust Impairs Nitric Oxide-Mediated Endothelial Vasomotor Function by Increasing Endothelial Oxidative Stress. Hypertension 2013; 62: 352-358.
9 Kaplan ZS, Jackson SP. The role of platelets in atherothrombosis. Hematology Am Soc Hematol Educ Program 2011; 2011: 51-61.
10 Nemmar A, Hoet PHM, Dinsdale D. et al. Diesel exhaust particles in lung acutely enhance experimental peripheral thrombosis. Circulation 2003; 107: 1202-1208.
11 Lucking AJ, Lundback M, Mills NL. et al. Diesel exhaust inhalation increases thrombus formation in man. Eur Heart J 2008; 29: 3043-3051.
12 Jacobs L, Emmerechts J, Mathieu C. et al. Air pollution related prothrombotic changes in persons with diabetes. Environ Health Perspect 2010; 118: 191-196.
13 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: 1075-1082.
14 Murakami T, Komiyama Y, Masuda M. et al. Flow cytometric analysis of platelet activation markers CD62P and CD63 in patients with coronary artery disease. Eur J Clin Invest 1996; 26: 996-1003.
15 Preston RA, Coffey JO, Materson BJ. et al. Elevated platelet P-selectin expression and platelet activation in high risk patients with uncontrolled severe hypertension. Atherosclerosis 2007; 192: 148-154.
16 Barath S, Mills NL, Lundbäck M. et al. Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions. Part Fibre Toxicol 2010; 7-19..
17 Choudhury A, Chung I, Blann AD. et al. Platelet surface CD62P and CD63, mean platelet volume, and soluble/platelet P-selectin as indexes of platelet function in atrial fibrillation: a comparison of “healthy control subjects” and “disease control subjects” in sinus rhythm. J Am Coll Cardiol 2007; 49: 1957-1964.
18 Rauch U, Ziegler D, Piolot R. et al. Platelet activation in diabetic cardiovascular autonomic neuropathy. Diabet Med 1999; 16: 848-852.
19 Gardner B, Ling F, Hopke PK. et al. Ambient fine particulate air pollution triggers ST-elevation myocardial infarction, but not non-ST elevation myo-cardial infarction: a case-crossover study. Part Fibre Toxicol 2014; 11: 1.
20 McEver RP, Cummings RD. Perspectives series: cell adhesion in vascular biology. Role of PSGL-1 binding to selectins in leukocyte recruitment. J Clin Invest 1997; 100: 485-491.
21 Siscovick DS, Weiss NS, Fletcher RH. et al. Habitual vigorous exercise and primary cardiac arrest: effect of other risk factors on the relationship. J Chronic Dis 1984; 37: 625-631.
22 Hilberg T, Glä D, Schmidt V. et al. Short-term exercise and platelet activity, sensitivity to agonist, and platelet-leukocyte conjugate formation. Platelets 2003; 14: 67-74.
23 World Health Organization. The world health report 2002 - Reducing Risks,. Promoting Healthy Life 2002; pp. 67-77.
24 Nemmar A, Nemery B, Hoet PHM. et al. Pulmonary inflammation and throm-bogenicity caused by diesel particles in hamsters: role of histamine. Am J Respir Crit Care Med 2003; 168: 1366-1372.
25 Van Hinsbergh VWM. Endothelium-role in regulation of coagulation and inflammation. Semin Immunopathol 2012; 34: 93-106.
26 Feron O, Balligand J-L. Caveolins and the regulation of endothelial nitric oxide synthase in the heart. Cardiovasc Res 2006; 69: 788-797.