Up-regulation of tissue factor in human pulmonary artery endothelial cells after ultrafine particle exposure.
BACKGROUND
Epidemiology studies have linked exposure to pollutant particles to increased cardiovascular mortality and morbidity, but the mechanisms remain unknown.


OBJECTIVE
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 microg/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 100 microg/mLUFP 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.
Karoly
Edward D
ED
National Health and Environmental Effects Research Laboratory, Office of Research and Development, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711, USA. karoly.edward@epa.gov
Li
Zhuowei
Z
Dailey
Lisa A
LA
Hyseni
Xhevahire
X
Huang
Yuh-Chin T
YC
D000393:Air Pollutants / Q000633:toxicity*; D001777:Blood Coagulation / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation; D010316:Particle Size; D011651:Pulmonary Artery / Q000166:cytology; D015854:Up-Regulation / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity
D000393:Air Pollutants; D001335:Vehicle Emissions