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Exposure to Diesel Exhaust Enhances the Generation of Vascular Microparticles
Citation:
BAILEY, C., M. M. Aleman, J. M. SOUKUP, J. C. Lay, AND M. S. CARRAWAY. Exposure to Diesel Exhaust Enhances the Generation of Vascular Microparticles. Presented at Arteriosclerosis, Thrombosis, and Vascular Biology 2011 Scientific Sessions, Chicago, IL, April 28 - 30, 2011.
Impact/Purpose:
This may provide mechanistic insight into air pollution induced cardiovascular effects and further evaluate the potential of MPs as a clinically relevant biomarker for air pollution.
Description:
Introduction: In the study of the health impacts of traffic-related air pollution, diesel exhaust is a pollutant of particular interest, since it is a major source of particulate matter (PM). Epidemiological studies associate exposure to ambient levels of PM with cardiovascular morbidity and mortality. However, the biological mechanisms by which PM exposure induces cardiovascular effects remain to be elucidated. Vascular microparticles (MP), 0.1-1 um microvesicles released by activated cells, are a potential clinical marker for cardiovascular dysfunction. MPs can promote coagulation and increased levels may indicate vascular injury, both hallmarks of cardiovascular disease. Objective: To determine if diesel exhaust particle (DEP) extracts induce the generation of vascular MPs that may promote coagulation. Methods: Venous blood was collected from normal healthy volunteers (N=6), anti-coagulated and exposed ex vivo for 6 hours to extracts of DEP that varied in organic content arret were from four different engine sources. MPs were isolated from the plasma, enumerated and characterized by flow cytometry. The coagulation potential of the MPs was assessed by tissue factor (TF) activity and thrombin generation. Results: Compared to MPs from vehicle-treated blood, two of four DEP extracts significantly augmented the generation of phosphatidylserine expressing MPs from vascular cells (2.1-3-fold, P<0.05). Three of the DEP sources induced a considerable amount of MPs derived from neutrophils (4.5-5.2- fold, P<0.05) compared to vehicle-exposed MPs. Two of these DEPs also increased monocyte-derived MPs (2.3-2.5 fold, P<0.05) and TF expressing monocyte MPs (1.5-1.8 fold, P<0.05). These same DEP-generated MPs had enhanced prothrombinase activity with a 1.4-1.5 fold increase in thrombin generation (nM/min). Conclusions: This analysis demonstrates that DEPs with a medium to high organic content illicit increased MP generation and promote the prothrombotic phenotype of MPs. This may provide mechanistic insight into air pollution induced cardiovascular effects and further evaluate the potential of MPs as a clinically relevant biomarker for air pollution. THIS ABSTRACT OF A PROPOSED PRESENTATION DOES NOT NECESSARILY REFLECT EPA POLICY.