Extracellular histones mediate the effects of metal-rich air particles on blood coagulation

L. Cantone, L. Angelici, V. Bollati, M. Bonzini, P. Apostoli, A. Tripodi, P. A. Bertazzi, A. A. Baccarelli

Research output: Contribution to journalArticle

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Abstract

Background: Epidemiological studies have shown associations of particulate matter (PM) exposure with hypercoagulability and thrombosis. Extracellular circulating histones have recently been identified as novel mediators of inflammatory and procoagulant responses. The potential roles of extracellular histones in PM-related hypercoagulability have yet not been investigated. Objectives: In 63 steel workers, we evaluated the effects of exposure to PM and PM metal components on two extracellular histone modifications (H3K4me3 and H3K9ac); and the association of H3K4me3 and H3K9ac with coagulation markers. Methods: Extracellular H3K4me3 and H3K9ac were determined in plasma through enzyme-linked immunosorbent assays. Coagulation markers included endogenous thrombin potentials (ETPs), tissue-type plasminogen activator antigen (t-PA) and d-dimer. Exposure to PM with aerodynamic diameters 1) or 10) and PM10 metal components were estimated for each participant. Results: The coagulation marker ETP, measured in the presence of soluble thrombomodulin (ETP TM+), showed significant positive associations with PM1 (β=107.84, p=0.03), PM10 (β=83.06, p=0.02), and zinc (β=75.14, p=0.03); and a marginal association with iron (β=122.58, p=0.07). Additional PM effects were observed on t-PA, D-dimer, and ETP TM+. PM1 exposure was associated with increased plasma H3K4me3 and H3K9ac (β=0.20, p=0.02; β=0.16, p=0.05, respectively). H3K4me3, but not H3K9ac, was associated with zinc (β=0.13, p=0.03) and iron (β=0.32, p=0.01) contained in PM. ETP TM+ was increased in association with higher plasma H3K4me3 (β=0.50, p=0.05) and H3K9ac (β=0.54, p=0.05). Conclusions: This observational study suggests potential roles of extracellular histones in PM-induced hypercoagulability. Experimental studies are warranted to further characterize these findings.

Original languageEnglish
Pages (from-to)76-82
Number of pages7
JournalEnvironmental Research
Volume132
DOIs
Publication statusPublished - 2014

Fingerprint

Particulate Matter
Blood Coagulation
Coagulation
coagulation
Histones
particulate matter
Blood
blood
Metals
Air
Thrombin
metal
air
Thrombophilia
Association reactions
antigen
Plasmas
plasma
Zinc
Histone Code

Keywords

  • Blood coagulation
  • Histones
  • Metals
  • Particulate matter
  • Thrombosis

ASJC Scopus subject areas

  • Environmental Science(all)
  • Biochemistry

Cite this

Extracellular histones mediate the effects of metal-rich air particles on blood coagulation. / Cantone, L.; Angelici, L.; Bollati, V.; Bonzini, M.; Apostoli, P.; Tripodi, A.; Bertazzi, P. A.; Baccarelli, A. A.

In: Environmental Research, Vol. 132, 2014, p. 76-82.

Research output: Contribution to journalArticle

Cantone, L. ; Angelici, L. ; Bollati, V. ; Bonzini, M. ; Apostoli, P. ; Tripodi, A. ; Bertazzi, P. A. ; Baccarelli, A. A. / Extracellular histones mediate the effects of metal-rich air particles on blood coagulation. In: Environmental Research. 2014 ; Vol. 132. pp. 76-82.
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abstract = "Background: Epidemiological studies have shown associations of particulate matter (PM) exposure with hypercoagulability and thrombosis. Extracellular circulating histones have recently been identified as novel mediators of inflammatory and procoagulant responses. The potential roles of extracellular histones in PM-related hypercoagulability have yet not been investigated. Objectives: In 63 steel workers, we evaluated the effects of exposure to PM and PM metal components on two extracellular histone modifications (H3K4me3 and H3K9ac); and the association of H3K4me3 and H3K9ac with coagulation markers. Methods: Extracellular H3K4me3 and H3K9ac were determined in plasma through enzyme-linked immunosorbent assays. Coagulation markers included endogenous thrombin potentials (ETPs), tissue-type plasminogen activator antigen (t-PA) and d-dimer. Exposure to PM with aerodynamic diameters 1) or 10) and PM10 metal components were estimated for each participant. Results: The coagulation marker ETP, measured in the presence of soluble thrombomodulin (ETP TM+), showed significant positive associations with PM1 (β=107.84, p=0.03), PM10 (β=83.06, p=0.02), and zinc (β=75.14, p=0.03); and a marginal association with iron (β=122.58, p=0.07). Additional PM effects were observed on t-PA, D-dimer, and ETP TM+. PM1 exposure was associated with increased plasma H3K4me3 and H3K9ac (β=0.20, p=0.02; β=0.16, p=0.05, respectively). H3K4me3, but not H3K9ac, was associated with zinc (β=0.13, p=0.03) and iron (β=0.32, p=0.01) contained in PM. ETP TM+ was increased in association with higher plasma H3K4me3 (β=0.50, p=0.05) and H3K9ac (β=0.54, p=0.05). Conclusions: This observational study suggests potential roles of extracellular histones in PM-induced hypercoagulability. Experimental studies are warranted to further characterize these findings.",
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T1 - Extracellular histones mediate the effects of metal-rich air particles on blood coagulation

AU - Cantone, L.

AU - Angelici, L.

AU - Bollati, V.

AU - Bonzini, M.

AU - Apostoli, P.

AU - Tripodi, A.

AU - Bertazzi, P. A.

AU - Baccarelli, A. A.

PY - 2014

Y1 - 2014

N2 - Background: Epidemiological studies have shown associations of particulate matter (PM) exposure with hypercoagulability and thrombosis. Extracellular circulating histones have recently been identified as novel mediators of inflammatory and procoagulant responses. The potential roles of extracellular histones in PM-related hypercoagulability have yet not been investigated. Objectives: In 63 steel workers, we evaluated the effects of exposure to PM and PM metal components on two extracellular histone modifications (H3K4me3 and H3K9ac); and the association of H3K4me3 and H3K9ac with coagulation markers. Methods: Extracellular H3K4me3 and H3K9ac were determined in plasma through enzyme-linked immunosorbent assays. Coagulation markers included endogenous thrombin potentials (ETPs), tissue-type plasminogen activator antigen (t-PA) and d-dimer. Exposure to PM with aerodynamic diameters 1) or 10) and PM10 metal components were estimated for each participant. Results: The coagulation marker ETP, measured in the presence of soluble thrombomodulin (ETP TM+), showed significant positive associations with PM1 (β=107.84, p=0.03), PM10 (β=83.06, p=0.02), and zinc (β=75.14, p=0.03); and a marginal association with iron (β=122.58, p=0.07). Additional PM effects were observed on t-PA, D-dimer, and ETP TM+. PM1 exposure was associated with increased plasma H3K4me3 and H3K9ac (β=0.20, p=0.02; β=0.16, p=0.05, respectively). H3K4me3, but not H3K9ac, was associated with zinc (β=0.13, p=0.03) and iron (β=0.32, p=0.01) contained in PM. ETP TM+ was increased in association with higher plasma H3K4me3 (β=0.50, p=0.05) and H3K9ac (β=0.54, p=0.05). Conclusions: This observational study suggests potential roles of extracellular histones in PM-induced hypercoagulability. Experimental studies are warranted to further characterize these findings.

AB - Background: Epidemiological studies have shown associations of particulate matter (PM) exposure with hypercoagulability and thrombosis. Extracellular circulating histones have recently been identified as novel mediators of inflammatory and procoagulant responses. The potential roles of extracellular histones in PM-related hypercoagulability have yet not been investigated. Objectives: In 63 steel workers, we evaluated the effects of exposure to PM and PM metal components on two extracellular histone modifications (H3K4me3 and H3K9ac); and the association of H3K4me3 and H3K9ac with coagulation markers. Methods: Extracellular H3K4me3 and H3K9ac were determined in plasma through enzyme-linked immunosorbent assays. Coagulation markers included endogenous thrombin potentials (ETPs), tissue-type plasminogen activator antigen (t-PA) and d-dimer. Exposure to PM with aerodynamic diameters 1) or 10) and PM10 metal components were estimated for each participant. Results: The coagulation marker ETP, measured in the presence of soluble thrombomodulin (ETP TM+), showed significant positive associations with PM1 (β=107.84, p=0.03), PM10 (β=83.06, p=0.02), and zinc (β=75.14, p=0.03); and a marginal association with iron (β=122.58, p=0.07). Additional PM effects were observed on t-PA, D-dimer, and ETP TM+. PM1 exposure was associated with increased plasma H3K4me3 and H3K9ac (β=0.20, p=0.02; β=0.16, p=0.05, respectively). H3K4me3, but not H3K9ac, was associated with zinc (β=0.13, p=0.03) and iron (β=0.32, p=0.01) contained in PM. ETP TM+ was increased in association with higher plasma H3K4me3 (β=0.50, p=0.05) and H3K9ac (β=0.54, p=0.05). Conclusions: This observational study suggests potential roles of extracellular histones in PM-induced hypercoagulability. Experimental studies are warranted to further characterize these findings.

KW - Blood coagulation

KW - Histones

KW - Metals

KW - Particulate matter

KW - Thrombosis

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