Comparative effects of inhaled diesel exhaust and ambient fine particles on inflammation, atherosclerosis, and vascular dysfunction.
Ambient air PM(2.5) (particulate matter less than 2.5 mum in diameter) has been associated with cardiovascular diseases (CVDs), but the underlying mechanisms affecting CVDs are unknown. The authors investigated whether subchronic inhalation of concentrated ambient PM(2.5) (CAPs), whole diesel exhaust (WDE), or diesel exhaust gases (DEGs) led to exacerbation of atherosclerosis, pulmonary and systemic inflammation, and vascular dysfunction; and whether DEG interactions with CAPs alter cardiovascular effects. ApoE(-/-) mice were simultaneously exposed via inhalation for 5 hours/day, 4 days/week, for up to 5 months to one of five different exposure atmospheres: (1) filtered air (FA); (2) CAPs (105 microg/m(3)); (3) WDE (DEP = 436 microg/m(3)); (4) DEG (equivalent to gas levels in WDE group); and (5) CAPs+DEG (PM(2.5): 113 microg/m(3); with DEG equivalent to WDE group). After 3 and 5 months, lung lavage fluid and blood sera were analyzed, and atherosclerotic plaques were quantified by ultrasound imaging, hematoxylin and eosin (H&E stain), and en face Sudan IV stain. Vascular functions were assessed after 5 months of exposure. The authors showed that (1) subchronic CAPs, WDE, and DEG inhalations increased serum vascular cell adhesion molecule (VCAM)-1 levels and enhanced phenylephrine (PE)-induced vasoconstriction; (2) for plaque exacerbation, CAPs > WDE > DEG = FA, thus PM components (not present in WDE) were responsible for plaque development; (3) atherosclerosis can exacerbated through mechanistic pathways other than inflammation and vascular dysfunction; and (4) although there were no significant interactions between CAPs and DEG on plaque exacerbation, it is less clear whether the effects of CAPs on vasomotor dysfunction and pulmonary/systemic inflammation were enhanced by the DEG coexposure.
Quan
Chunli
C
Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.
Sun
Qinghua
Q
Lippmann
Morton
M
Chen
Lung-Chi
LC
D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000473:pathology; D050197:Atherosclerosis / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology; D016122:Brachiocephalic Trunk / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D002316:Cardiotonic Agents; D004357:Drug Synergism; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D052638:Particulate Matter / Q000633:toxicity*; D011014:Pneumonia / Q000139:chemically induced / Q000473:pathology; D014463:Ultrasonography; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014666:Vasomotor System; D001335:Vehicle Emissions / Q000633:toxicity*
D000393:Air Pollutants; D002316:Cardiotonic Agents; D052638:Particulate Matter; D019010:Vascular Cell Adhesion Molecule-1; D001335:Vehicle Emissions
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