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 µm in aerodynamic diameter), PM1 (≤1 µm) and air metal components. We determined leukocyte DNA methylation of NOS3 (nitric-oxide-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.
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 µm in aerodynamic diameter), PM1 (≤1 µm) and air metal components. We determined leukocyte DNA methylation of NOS3 (nitric-oxide-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.
Authors: Zhong-Zheng Zhu; Lifang Hou; Valentina Bollati; Letizia Tarantini; Barbara Marinelli; Laura Cantone; Allen S Yang; Pantel Vokonas; Jolanta Lissowska; Silvia Fustinoni; Angela C Pesatori; Matteo Bonzini; Pietro Apostoli; Giovanni Costa; Pier Alberto Bertazzi; Wong-Ho Chow; Joel Schwartz; Andrea Baccarelli Journal: Int J Epidemiol Date: 2010-09-15 Impact factor: 7.196
Authors: S Wielders; M Mukherjee; J Michiels; D T Rijkers; J P Cambus; R W Knebel; V Kakkar; H C Hemker; S Béguin Journal: Thromb Haemost Date: 1997-04 Impact factor: 5.249
Authors: Olivier Segers; René van van Oerle; Hugo ten ten Cate; Jan Rosing; Elisabetta Castoldi Journal: Thromb Haemost Date: 2009-11-13 Impact factor: 5.249
Authors: L Cantone; L Angelici; V Bollati; M Bonzini; P Apostoli; A Tripodi; P A Bertazzi; A A Baccarelli Journal: Environ Res Date: 2014-04-16 Impact factor: 6.498