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UP-REGULATION OF TISSUE FACTOR IN HUMAN PULMONARY ARTERY ENDOTHELIAL CELLS AFTER ULTRAFINE PARTICLE EXPOSURE
Citation:
KAROLY, E., Z. LI, L. A. DAILEY, J. HYSENI, AND Y. T. HUANG. UP-REGULATION OF TISSUE FACTOR IN HUMAN PULMONARY ARTERY ENDOTHELIAL CELLS AFTER ULTRAFINE PARTICLE EXPOSURE. ENVIRONMENTAL HEALTH PERSPECTIVES. National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, NC, 115(4):535-540, (2007).
Impact/Purpose:
To test the hypothesis that the ultrafine fraction of ambient pollutant particles would cause endothelial cells dysfunction
Description:
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 cells dysfunction.
Methods: We profiled gene expression of human pulmonary artery endothelial cells
(HPAEC) exposed to ultrafine Chapel Hill particles (UFP) (100µg/ml) or vehicle for 4h
with Affymetrix HG U133 Plus 2.0 chips (N = 4 each).
Results: Using an unpaired t-test (p <0.01, 5% false discovery rate) we found 320
upregulated genes and 106 downregulated genes. These genes included those in the CXC
chemokine family that have been implicated in the pathogenesis of vascular disease
(MCP-1, IL-8, CXCL1, CXCL2, CXCL3 and CXCR4). We also noted upregulation of
genes related to coagulation (tissue factor [F3] and coagulation factor II receptor-like 2
[F2RL2, PAR3]) and differential regulation of genes related to F3 signaling (FOS, JUN
and NFKBIA). Both the water-soluble and water-insoluble fractions of UFP increased the
expression of F3, F2RL2 and heme oxygenase 1 (HMOX1). Treatment of HPAEC with
UFP for 16 hours increased the release of 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 uncovered that UFP may induce vascular
endothelial cells to express genes related to clotting and angiogenesis. These results
provide a novel hypothesis that PM may cause cardiovascular adverse health effects by
activating coagulation-inflammation circuitry.