title: In Utero Exposure of Hyperlipidemic Mice to Diesel Exhaust: Lack of Effects on Atherosclerosis in Adult Offspring Fed a Regular Chow Diet.
abstract: Uterine stress is associated with an increased risk of later life metabolic diseases. In this study, we investigated the effect of diesel exhaust (DE) exposure in utero on adult susceptibility to atherosclerosis in genetically hyperlipidemic mice. Pregnant apolipoprotein E-deficient mice received either DE exposure (~250-300 μg/m3PM2.5for 6 h/day, 5 days/week) or filtered air (FA) throughout gestation. Treatment effects on litter size and gender distribution were recorded. Plasma cholesterol and triglycerides were measured at 8, 12 and 16 weeks of age. Urinary 8-isoprostane and liver 8-hydroxy-deoxyguanosine levels were measured at killing at 16 weeks of age. Expression of the antioxidant genes heme oxygenase-1 and the glutamate-cysteine ligase modifier and catalytic subunits were measured in the lung, liver and aorta. The average area and frequency of atherosclerotic lesions were measured in the aortic sinus and innominate arteries. There were significantly smaller litters and higher postnatal mortality in the DE-exposed mice. There were no significant differences in plasma lipids or lipoprotein profiles, expression of antioxidant genes or markers of oxidative stress between treatment groups. There were also no significant differences in average atherosclerotic lesion area in the aortic sinus or innominate arteries of the DE and FA groups although there was a higher frequency of lesions in the DE-exposed group. Our study indicates that in utero DE exposure does not influence later life lipoprotein metabolism, redox homeostasis or the risk of developing larger atherosclerotic lesions.
authors.affiliation: Program in Nutritional Sciences, University of Washington, Box 358050, Seattle, WA, 98109-4714, USA.
authors.forename: Jenna
authors.initials: J
authors.lastname: Harrigan
authors.affiliation: Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA.
authors.forename: Divya
authors.initials: D
authors.lastname: Ravi
authors.affiliation: Department of Pathology, University of Washington, Seattle, WA, USA.
authors.forename: Jerry
authors.initials: J
authors.lastname: Ricks
authors.affiliation: Program in Nutritional Sciences, University of Washington, Box 358050, Seattle, WA, 98109-4714, USA. ssmjm@uw.edu.|Department of Environmental and Occupational Health Sciences, University of Washington, Seattle, WA, USA. ssmjm@uw.edu.|Department of Pathology, University of Washington, Seattle, WA, USA. ssmjm@uw.edu.
authors.forename: Michael E
authors.identifier: http://orcid.org/0000-0003-2784-4345
authors.initials: ME
authors.lastname: Rosenfeld
mesh_terms: D000367:Age Factors; D000821:Animal Feed; D000818:Animals; D050197:Atherosclerosis / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006949:Hyperlipidemias / Q000097:blood* / Q000473:pathology; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood* / Q000473:pathology; D014280:Triglycerides / Q000097:blood; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D008074:Lipoproteins; D014280:Triglycerides; D001335:Vehicle Emissions
keywords: Air pollution; Apo E-deficient mice; Atherosclerosis; Diesel exhaust; Intrauterine stress