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GENE EXPRESSION PROFILES IN HUMAN AND RAT VASCULAR ENDOTHELIAL CELLS EXPOSED TO RESIDUAL OIL FLY ASH (ROFA) AND VANADIUM (V)
Citation:
Nadadur, S. S., D. W. Winsett, AND D L. Costa. GENE EXPRESSION PROFILES IN HUMAN AND RAT VASCULAR ENDOTHELIAL CELLS EXPOSED TO RESIDUAL OIL FLY ASH (ROFA) AND VANADIUM (V). Presented at Lovelace Respiratory Research Institute Annual Symposium, Albuquerque, NM, Oct. 13-17, 2002.
Description:
Gene expression profiles in human and rat vascular endothelial cells exposed to residual oil fly ash (ROFA) or vanadium (V).
Srikanth S. Nadadur, Darrell W. Winsett and Daniel L. Costa, US EPA, ORD, NHEERL (ETD, Pulmonary Toxicology Branch), Research Triangle Park, NC 27711.
Epidemiological studies have reported increased mortality and morbidity in cardiopulmonary patients with increased levels of particulate matter (PM) in the environment. The mechanisms of action for PM and the constituents responsible for the observed health effects are not known. Recent studies implicating cardiovascular and clotting systems in PM response suggest that the vascular endothelium may be targeted. To test this hypothesis and understand the possible role of endothelial dysfunction in PM cardiovascular toxicity, we initiated studies with primary vascular endothelial cell cultures using a model PM, ROFA, and one of its toxic metal constituents, V. Assessing the temporal differential expression of genes on acute exposure to ROFA or V could reveal the transcriptional regulation involved in the initiation and progression of acute injury. Primary cultures of human umbilical vein endothelial cells (HUVEC) and rat pulmonary micro-vessel endothelial cells (RLMVEC) (VEC Technologies, Inc., New York, NY) were exposed to saline, ROFA (1mg/ml) or V (1mM) for 25 minutes to investigate the immediate injury and/or stress response. Global gene expression profiles were generated using human (8k) and rat (4k) plastic microarrays (Clontech, Palo Alto, CA). Analysis of the gene expression data (GeneSpring, Silicon Genetics, Redwood City, CA) indicated exposure and species-specific differential gene expression and altered genes can be grouped into genes common to both the treatments as well as unique to ROFA and V exposure. Classification of altered genes based on biological processes, cellular components and molecular function indicated species-specific differences in ROFA and V toxicity. Despite species differences, the differential gene expression profiles observed here suggest direct toxic effects of ROFA and V on endothelial cells and their possible involvement in cardiovascular effects of PM. (This abstract does not reflect US EPA policy).