Inhaled diesel emissions alter atherosclerotic plaque composition in ApoE(-/-) mice.
Recent epidemiological studies suggest that traffic-related air pollution may have detrimental effects on cardiovascular health. Previous studies reveal that gasoline emissions can induce several enzyme pathways involved in the formation and development of atherosclerotic plaques. As a direct comparison, the present study examined the impact of diesel engine emissions on these pathways, and further examined the effects on vascular lesion pathology. Apolipoprotein E-null mice were simultaneously placed on a high-fat chow diet and exposed to four concentrations, plus a high concentration exposure with particulates (PM) removed by filtration, of diesel emissions for 6 h/day for 50 days. Aortas were subsequently assayed for alterations in matrix metalloproteinase-9, endothelin-1, and several other biomarkers. Diesel induced dose-related alterations in gene markers of vascular remodeling and aortic lipid peroxidation; filtration of PM did not significantly alter these vascular responses, indicating that the gaseous portion of the exhaust was a principal driver. Immunohistochemical analysis of aortic leaflet sections revealed no net increase in lesion area, but a significant decrease in lipid-rich regions and increasing trends in macrophage accumulation and collagen content, suggesting that plaques were advanced to a more fragile, potentially more vulnerable state by diesel exhaust exposure. Combined with previous studies, these results indicate that whole emissions from mobile sources may have a significant role in promoting chronic vascular disease.
Campen
Matthew J
MJ
Toxicology Division, Lovelace Respiratory Research Institute, Albuquerque, NM, USA. mcampen@salud.unm.edu
Lund
Amie K
AK
Knuckles
Travis L
TL
Conklin
Daniel J
DJ
Bishop
Barbara
B
Young
David
D
Seilkop
Steven
S
Seagrave
JeanClare
J
Reed
Matthew D
MD
McDonald
Jacob D
JD
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology*; D003094:Collagen / Q000378:metabolism; D004041:Dietary Fats / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism; D007150:Immunohistochemistry; D019570:Inhalation Exposure; D015227:Lipid Peroxidation / Q000187:drug effects; D008264:Macrophages / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D001335:Vehicle Emissions / Q000633:toxicity*
D000393:Air Pollutants; D001057:Apolipoproteins E; D004041:Dietary Fats; D019332:Endothelin-1; D001335:Vehicle Emissions; D003094:Collagen; D020780:Matrix Metalloproteinase 9