Endothelial effects of emission source particles: acute toxic response gene expression profiles.
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 approximately 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.
Nadadur
Srikanth S
SS
Pulmonary Toxicology Branch, Experimental Toxicology Division, National Health Environmental Effects Research Laboratory, ORD, US EPA, Research Triangle Park, NC 27711, USA. Nadadurs@niehs.nih.gov
Haykal-Coates
Najwa
N
Mudipalli
Anuradha
A
Costa
Daniel L
DL
D000393:Air Pollutants / Q000633:toxicity*; D002244:Carbon / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D060729:Coal Ash; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D052638:Particulate Matter / Q000633:toxicity*; D023382:Toxicity Tests, Acute; D014471:Umbilical Veins / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D014639:Vanadium / Q000633:toxicity
D000393:Air Pollutants; D060729:Coal Ash; D052638:Particulate Matter; D014639:Vanadium; D002244:Carbon