| Up-regulation of Tissue Factor in Human Pulmonary Artery Endothelial Cells after Ultrafine Particle Exposure Edward D. Karoly,1 Zhuowei Li,2 Lisa A. Dailey,1 Xhevahire Hyseni,1 and Yuh-Chin T. Huang1,3 1National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA; 2Center for Environmental Medicine, Asthma and Lung Biology, University of North Carolina, Chapel Hill, North Carolina, USA; 3Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA Abstract
Background: Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, but the mechanisms remain unknown. Objectives: We tested the hypothesis that the ultrafine fraction of ambient pollutant particles would cause endothelial cell dysfunction. Methods: We profiled gene expression of human pulmonary artery endothelial cells (HPAEC) exposed to ultrafine particles (UFPs ; 100 µg/mL) from Chapel Hill, North Carolina, or vehicle for 4 hr with Affymetrix HG U133 Plus 2.0 chips (n = 4 each) . Results: We found 320 up-regulated genes and 106 down-regulated genes (p < 0.01, 5% false discovery rate) . We noted up-regulation of genes related to coagulation [tissue factor (F3) and coagulation factor II receptor-like 2 (F2RL2) ] and differential regulation of genes related to F3 signaling (FOS, JUN, and NFKBIA) . Results of quantitative polymerase chain reaction show a significant up-regulation of F3 after 10 and 100µg/mL UFP exposures. Additionally, the water-soluble fractions of UFPs were sufficient to induce the expression of F3, F2RL2, and heme oxygenase 1 (HMOX1) . Treatment of HPAEC with UFPs for 16 hr increased the release of interleukin (IL) -6 and IL-8. Pretreatment of HPAEC with a blocking antibody against F3 attenuated IL-6 and IL-8 release by 30 and 70%, respectively. Conclusions: Using gene profiling, we discovered that UFPs may induce vascular endothelial cells to express genes related to clotting. These results indicate that PM may cause adverse cardiovascular health effects by activating coagulation-inflammation circuitry. Key words: coagulation cascade, human endothelial cells, microarray, particulate matter, tissue factor. Environ Health Perspect 115:535–540 (2007) . doi:10.1289/ehp.9556 available via http://dx.doi.org/ [Online 8 January 2007]
Address correspondence to E.D. Karoly, MD-58D, U.S. EPA, Research Triangle Park, NC 27711 USA. Telephone: (919) 843-8031. Fax: (919) 966-6271. E-mail: karoly.edward@epa.gov The research described in this article has been reviewed by the U.S. EPA National Health Effects and Environmental Research Laboratory and has been approved for publication. Approval does not signify that the contents necessarily reflect the views and policies of the U.S. EPA, nor does mention of the trade names or commercial products constitute endorsement or recommendation for use. The authors declare they have no competing financial interests. Received 27 July 2006 ; accepted 8 January 2007.
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