Effect of ambient particulate matter exposure on hemostasis.
Epidemiological studies have linked levels of particulate matter (PM) in ambient air to cardiovascular mortality and hospitalizations for myocardial infarction (MI) and stroke. Thrombus formation plays a primary role in potentiating acute cardiovascular events, and this study was undertaken to determine whether pulmonary exposure to PM alters hemostasis. PM was collected from the Chapel Hill, NC airshed and was administered to mice by intratracheal instillation at a dose previously shown to exacerbate myocardial ischemia-reperfusion injury. Twenty-four hours after exposure, an increase occurred in the number of circulating platelets and plasma concentrations of fibrinogen and soluble P-selectin. The concentration of tissue factor pathway inhibitor (TFPI) in plasma was decreased, whereas the plasma concentration of plasminogen activator inhibitor (PAI-1) was increased. Consistent with these observations, bleeding time from a tail-tip transection was shortened. These results provide evidence that PM exposure alters hemostasis in otherwise healthy animals and may thereby promote clot formation and impede clot resolution in susceptible individuals. The results also establish definite hemostatic endpoints that can be used to further investigate the effects of dose and particle characteristics on the toxicity of ambient particles.
Cozzi
Emily
E
Department of Physiology, Brody School of Medicine at East Carolina University, Greenville, NC 27834, USA.
Wingard
Christopher J
CJ
Cascio
Wayne E
WE
Devlin
Robert B
RB
Miles
Jeremy J
JJ
Bofferding
April R
AR
Lust
Robert M
RM
Van Scott
Michael R
MR
Henriksen
Ruth Ann
RA
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001760:Bleeding Time; D001792:Blood Platelets / Q000187:drug effects; D005340:Fibrinogen / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects*; D019570:Inhalation Exposure; D007442:Intubation, Intratracheal; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D019007:P-Selectin / Q000097:blood; D052638:Particulate Matter / Q000633:toxicity*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood
D000393:Air Pollutants; D008074:Lipoproteins; D019007:P-Selectin; D052638:Particulate Matter; D017395:Plasminogen Activator Inhibitor 1; C051928:lipoprotein-associated coagulation inhibitor; D005340:Fibrinogen