PMID- 17065432 OWN - NLM STAT- MEDLINE DCOM- 20070405 LR - 20161124 IS - 1096-6080 (Print) IS - 1096-0929 (Linking) VI - 95 IP - 2 DP - 2007 Feb TI - Gasoline exhaust emissions induce vascular remodeling pathways involved in atherosclerosis. PG - 485-94 AB - Epidemiological evidence indicates that environmental air pollutants are positively associated with the development of chronic vascular disease; however, the mechanisms involved have not been fully elucidated. In the present study we examined molecular pathways associated with chronic vascular disease in atherosclerosis-prone apolipoprotein E-deficient (ApoE(-/-)) mice, including markers of vascular remodeling and oxidative stress, in response to exposure to the ubiquitous environmental pollutant, gasoline engine emissions. ApoE(-/-) mice, on a high-fat diet, were exposed by inhalation to either filtered air; 8, 40, or 60 mug/m(3) particulate matter whole exhaust; or filtered exhaust with gases matching the 60-mug/m(3) concentration, for 7 weeks. Aortas and plasma were collected and assayed for changes in histochemical markers, real-time reverse transcriptase-polymerase chain reaction, and indicators of oxidative damage. Inhalational exposure to gasoline engine emissions resulted in increased aortic mRNA expression of matrix metalloproteinase-3 (MMP-3), MMP-7, and MMP-9, tissue inhibitor of metalloproteinases-2, endothelin-1 and heme oxygenase-1 in ApoE(-/-) mice; increased aortic MMP-9 protein levels were confirmed through immunohistochemistry. Elevated reactive oxygen species were also observed in arteries from exposed animals, despite absence of plasma markers. Similar findings were also observed in the aortas of ApoE(-/-) mice exposed to particle-filtered atmosphere, implicating the gaseous components of the whole exhaust in mediating the expression of markers associated with the vasculopathy. These findings demonstrate that exposure to gasoline engine emissions results in the transcriptional upregulation of factors associated with vascular remodeling, as well as increased markers of vascular oxidative stress, which may contribute to the progression of atherosclerosis and reduced stability of vulnerable plaques. FAU - Lund, Amie K AU - Lund AK AD - Division of Toxicology, Lovelace Respiratory Research Institute, 2425 Ridgecrest Drive SE, Albuquerque, New Mexico 87108, USA. FAU - Knuckles, Travis L AU - Knuckles TL FAU - Obot Akata, Chrys AU - Obot Akata C FAU - Shohet, Ralph AU - Shohet R FAU - McDonald, Jacob D AU - McDonald JD FAU - Gigliotti, Andrew AU - Gigliotti A FAU - Seagrave, Jean Clare AU - Seagrave JC FAU - Campen, Matthew J AU - Campen MJ LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20061025 PL - United States TA - Toxicol Sci JT - Toxicological sciences : an official journal of the Society of Toxicology JID - 9805461 RN - 0 (Air Pollutants) RN - 0 (Apolipoproteins E) RN - 0 (Dietary Fats) RN - 0 (Endothelin-1) RN - 0 (Reactive Oxygen Species) RN - 0 (Vehicle Emissions) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 3.4.- (Metalloproteases) SB - IM MH - Air Pollutants/*toxicity MH - Animals MH - Aorta/*drug effects/metabolism/pathology MH - Apolipoproteins E/genetics MH - *Atherosclerosis/etiology/metabolism/pathology MH - Dietary Fats/administration & dosage MH - Endothelin-1/biosynthesis MH - Heme Oxygenase-1/biosynthesis MH - Lung/*drug effects/metabolism/pathology MH - Male MH - Metalloproteases/biosynthesis MH - Mice MH - Mice, Knockout MH - Oxidative Stress/*drug effects/genetics MH - Reactive Oxygen Species/metabolism MH - Transcription, Genetic MH - Vehicle Emissions/*toxicity EDAT- 2006/10/27 09:00 MHDA- 2007/04/06 09:00 CRDT- 2006/10/27 09:00 PHST- 2006/10/27 09:00 [pubmed] PHST- 2007/04/06 09:00 [medline] PHST- 2006/10/27 09:00 [entrez] AID - kfl145 [pii] AID - 10.1093/toxsci/kfl145 [doi] PST - ppublish SO - Toxicol Sci. 2007 Feb;95(2):485-94. doi: 10.1093/toxsci/kfl145. Epub 2006 Oct 25.