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Endothelial Effects of Emission Source particles: Acute Toxic Response Gene Expression Profiles
Citation:
NADADUR, S. S., N. HAYKAL-COATES, A. MUDIPALLI, AND D. L. COSTA. Endothelial Effects of Emission Source particles: Acute Toxic Response Gene Expression Profiles. TOXICOLOGY IN VITRO. Elsevier Science Ltd, New York, NY, 23(1):67-77, (2009).
Impact/Purpose:
Ambient particulate matter (PM) is a heterogeneous mixture of liquid and/or solid materials suspended in the air, whose chemical composition and size vary over time and space. Although the composition of PM varies according to the geographical location of collection, PM contains many common constituent groups such as sulfates, nitrates, elemental carbon, organic carbon, pollen, endotoxins and various metals. From a regulatory perspective, PM in the ambient air is classified into two primary size modes (aerodynamic mass median diameters) based on their aerodynamic properties exploited during collection method.
Description:
Air pollution epidemiology has established a strong association between exposure to ambient particulate matter (PM) and cardiovascular outcomes. Experimental studies in both humans and laboratory animals support varied biological mechanisms including endothelial dysfunction as potentially a central step to the elicitation of cardiovascular events. We therefore hypothesized that relevant early molecular alterations on endothelial cells should be assessable in vitro upon acute exposure to PM components previously shown to be involved in health outcomes. Using a model emission PM, residual oil fly ash and one of its predominant constituents (vanadium - V), we focused on the development of gene expression profiles to fingerprint that particle and its constituents to explore potential biomarkers for PM-induced endothelial dysfunction. Here we present differential gene expression and transcription factor activation profiles in human vascular endothelial cells exposed to a non-cytotoxic dose of fly ash or V following semi-global gene expression profiling of ~8000 genes. Both fly ash and it’s prime constituent, V, induced alterations in genes involved in passive and active transport of solutes across the membrane; voltage-dependent ion pumps; induction of extracellular matrix proteins and adhesion molecules; and activation of numerous kinases involved in signal transduction pathways. These preliminary data suggest that cardiovascular effects associated with exposure to PM may be mediated by perturbations in endothelial cell permeability, membrane integrity; and ultimately endothelial dysfunction.