title: Exposure to acrolein by inhalation causes platelet activation.
abstract: Acrolein is a common air pollutant that is present in high concentrations in wood, cotton, and tobacco smoke, automobile exhaust and industrial waste and emissions. Exposure to acrolein containing environmental pollutants such as tobacco smoke and automobile exhaust has been linked to the activation of the coagulation and hemostasis pathways and thereby to the predisposition of thrombotic events in human. To examine the effects of acrolein on platelets, adult male C57Bl/6 mice were subjected acute (5ppm for 6h) or sub-chronic (1ppm, 6h/day for 4days) acrolein inhalation exposures. The acute exposure to acrolein did not cause pulmonary inflammation and oxidative stress, dyslipidemia or induce liver damage or muscle injury. Platelet GSH levels in acrolein-exposed mice were comparable to controls, but acrolein-exposure increased the abundance of protein-acrolein adducts in platelets. Platelets isolated from mice, exposed to both acute and sub-chronic acrolein levels, showed increased ADP-induced platelet aggregation. Exposure to acrolein also led to an increase in the indices of platelet activation such as the formation of platelet-leukocyte aggregates in the blood, plasma PF4 levels, and increased platelet-fibrinogen binding. The bleeding time was decreased in acrolein exposed mice. Plasma levels of PF4 were also increased in mice exposed to environmental tobacco smoke. Similar to inhalation exposure, acrolein feeding to mice also increased platelet activation and established a pro-thrombotic state in mice. Together, our data suggest that acrolein is an important contributing factor to the pro-thrombotic risk in human exposure to pollutants such as tobacco smoke or automobile exhaust, or through dietary consumption.
authors.affiliation: Department of Physiology and Biophysics, University of Louisville, Louisville, KY 40202, USA.
authors.forename: Srinivas D
authors.initials: SD
authors.lastname: Sithu
authors.forename: Sanjay
authors.initials: S
authors.lastname: Srivastava
authors.forename: Maqsood A
authors.initials: MA
authors.lastname: Siddiqui
authors.forename: Elena
authors.initials: E
authors.lastname: Vladykovskaya
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Riggs
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Conklin
authors.forename: Petra
authors.initials: P
authors.lastname: Haberzettl
authors.forename: Timothy E
authors.initials: TE
authors.lastname: O'Toole
authors.forename: Aruni
authors.initials: A
authors.lastname: Bhatnagar
authors.forename: Stanley E
authors.initials: SE
authors.lastname: D'Souza
mesh_terms: D000171:Acrolein / Q000633:toxicity*; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D019570:Inhalation Exposure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D014028:Tobacco Smoke Pollution
chemical_list: D000393:Air Pollutants; D014028:Tobacco Smoke Pollution; D000171:Acrolein; D005340:Fibrinogen