Objectives Recent investigations have associated airborne particulate matter (PM) with increased coagulation and thrombosis, but underlying biological mechanisms are still incompletely characterised. DNA methylation is an environmentally sensitive mechanism of gene regulation that could potentially contribute to PM-induced hypercoagulability. We aimed to test whether altered methylation mediates environmental effects on coagulation. Methods We investigated 63 steel workers exposed to a wide range of PM levels, as a work-related condition with well-characterised prothrombotic exposure. We measured personal PM10 (PM≤10 mm in aerodynamic diameter), PM 1 (≤1 mm) and air metal components. We determined leukocyte DNA methylation of NOS3 (nitricoxide- synthase-3) and EDN1 (endothelin-1) through bisulfite-pyrosequencing and we measured ETP as a global coagulation-activation test after standardised triggers. Results ETP increased in association with PM10 (β=20.0, 95% CI 3.0 to 37.0), PM1 (β=80.8 95% CI 14.9 to 146.7) and zinc (β=51.3, 95% CI 0.01 to 111.1) exposures. NOS3 methylation was negatively associated with PM10 (β=-0.2, 95% CI -0.4 to -0.03), PM1 (β=-0.8, 95% CI -1.4 to -0.1), zinc (β=-0.9, 95% CI -1.4 to -0.3) and iron (β=-0.7, 95% CI -1.4 to -0.01) exposures. Zinc exposure was negatively associated with EDN1 (β=-0.3, 95% CI -0.8 to -0.1) methylation. Lower NOS3 (β=-42.3; p<0.001) and EDN1 (β=-14.5; p=0.05) were associated with higher ETP. Statistical mediation analysis formally confirmed NOS3 and EDN1 hypomethylation as intermediate mechanisms for PM-related coagulation effects. Conclusions Our study showed for the first time, that gene hypomethylation contributes to environmentally induced hypercoagulability.

Blood hypomethylation of inflammatory genes mediates the effects of metal-rich airborne pollutants on blood coagulation / L. Tarantini, M. Bonzini, A. Tripodi, L. Angelici, F. Nordio, L. Cantone, P. Apostoli, P.A. Bertazzi, A. Baccarelli. - In: OCCUPATIONAL AND ENVIRONMENTAL MEDICINE. - ISSN 1351-0711. - 70:6(2013), pp. 418-425. [10.1136/oemed-2012-101079]

Blood hypomethylation of inflammatory genes mediates the effects of metal-rich airborne pollutants on blood coagulation

L. Tarantini;M. Bonzini;A. Tripodi;L. Angelici;NORDIO, FRANCESCO;L. Cantone;P.A. Bertazzi;A. Baccarelli
2013

Abstract

Objectives Recent investigations have associated airborne particulate matter (PM) with increased coagulation and thrombosis, but underlying biological mechanisms are still incompletely characterised. DNA methylation is an environmentally sensitive mechanism of gene regulation that could potentially contribute to PM-induced hypercoagulability. We aimed to test whether altered methylation mediates environmental effects on coagulation. Methods We investigated 63 steel workers exposed to a wide range of PM levels, as a work-related condition with well-characterised prothrombotic exposure. We measured personal PM10 (PM≤10 mm in aerodynamic diameter), PM 1 (≤1 mm) and air metal components. We determined leukocyte DNA methylation of NOS3 (nitricoxide- synthase-3) and EDN1 (endothelin-1) through bisulfite-pyrosequencing and we measured ETP as a global coagulation-activation test after standardised triggers. Results ETP increased in association with PM10 (β=20.0, 95% CI 3.0 to 37.0), PM1 (β=80.8 95% CI 14.9 to 146.7) and zinc (β=51.3, 95% CI 0.01 to 111.1) exposures. NOS3 methylation was negatively associated with PM10 (β=-0.2, 95% CI -0.4 to -0.03), PM1 (β=-0.8, 95% CI -1.4 to -0.1), zinc (β=-0.9, 95% CI -1.4 to -0.3) and iron (β=-0.7, 95% CI -1.4 to -0.01) exposures. Zinc exposure was negatively associated with EDN1 (β=-0.3, 95% CI -0.8 to -0.1) methylation. Lower NOS3 (β=-42.3; p<0.001) and EDN1 (β=-14.5; p=0.05) were associated with higher ETP. Statistical mediation analysis formally confirmed NOS3 and EDN1 hypomethylation as intermediate mechanisms for PM-related coagulation effects. Conclusions Our study showed for the first time, that gene hypomethylation contributes to environmentally induced hypercoagulability.
Settore BIO/12 - Biochimica Clinica e Biologia Molecolare Clinica
Settore MED/15 - Malattie del Sangue
Settore MED/09 - Medicina Interna
Settore MED/44 - Medicina del Lavoro
OCCUPATIONAL AND ENVIRONMENTAL MEDICINE
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/219932
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