title: Components of ambient air pollution affect thrombin generation in healthy humans: the RAPTES project.
abstract: OBJECTIVE
  Increases in ambient particulate matter (PM) have been associated with an elevated risk of stroke, myocardial ischaemia and coronary heart disease, with activation of blood coagulation likely playing an important role. PM-mediated activation of two major activation pathways of coagulation provides a potential mechanism for the observed association between PM and cardiovascular disease. However, it remains unclear which specific characteristics and components of air pollution are responsible.
  
  
  METHODS
  In order to investigate those characteristics and components, we semiexperimentally exposed healthy adult volunteers at five different locations with increased contrasts and reduced correlations among PM characteristics. Volunteers were exposed for 5 h, exercising intermittently, 3-7 times at different sites from March to October 2009. On site, we measured PM mass and number concentration, its oxidative potential (OP), content of elemental/organic carbon, trace metals, sulphate, nitrate and gaseous pollutants (ozone, nitrogen oxides). Before and 2 and 18 h after exposure we sampled blood from the participants and measured thrombin generation using the calibrated automated thrombogram.
  
  
  RESULTS
  We found that thrombin generation increases in the intrinsic (FXII-mediated) blood coagulation pathway in relation to ambient air pollution exposure. The associations with NO2, nitrate and sulphate were consistent and robust, insensitive to adjustment for other pollutants. The associations with tissue factor-mediated thrombogenicity were not very consistent.
  
  
  CONCLUSIONS
  Ex vivo thrombin generation was associated with exposure to NO2, nitrate and sulphate, but not PM mass, PM OP or other measured air pollutants.
authors: Centre for Environmental Health (MGO), National Institute for Public Health and the Environment (RIVM), The Netherlands.
authors: Maciej
authors: M
authors: Strak
authors: Gerard
authors: G
authors: Hoek
authors: Maaike
authors: M
authors: Steenhof
authors: Evren
authors: E
authors: Kilinc
authors: Krystal J
authors: KJ
authors: Godri
authors: Ilse
authors: I
authors: Gosens
authors: Ian S
authors: IS
authors: Mudway
authors: René
authors: R
authors: van Oerle
authors: Henri M H
authors: HM
authors: Spronk
authors: Flemming R
authors: FR
authors: Cassee
authors: Frank J
authors: FJ
authors: Kelly
authors: Roy M
authors: RM
authors: Harrison
authors: Bert
authors: B
authors: Brunekreef
authors: Erik
authors: E
authors: Lebret
authors: Nicole A H
authors: NA
authors: Janssen
mesh_terms: D000328:Adult; D000393:Air Pollutants / Q000009:adverse effects* / Q000032:analysis; D000397:Air Pollution / Q000009:adverse effects* / Q000032:analysis; D001777:Blood Coagulation / Q000187:drug effects*; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced*; D004781:Environmental Exposure / Q000009:adverse effects* / Q000032:analysis; D015444:Exercise; D005260:Female; D006801:Humans; D008297:Male; D009566:Nitrates / Q000009:adverse effects / Q000032:analysis; D009569:Nitric Oxide / Q000009:adverse effects / Q000032:analysis; D052638:Particulate Matter / Q000009:adverse effects* / Q000032:analysis; D012016:Reference Values; D015398:Signal Transduction; D013431:Sulfates / Q000009:adverse effects / Q000032:analysis; D013917:Thrombin / Q000096:biosynthesis*; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced; D055815:Young Adult
chemical_list: D000393:Air Pollutants; D009566:Nitrates; D052638:Particulate Matter; D013431:Sulfates; D009569:Nitric Oxide; D013917:Thrombin