title: Particulate matter exposure induces persistent lung inflammation and endothelial dysfunction.
abstract: Epidemiologic and animal studies have shown that exposure to particulate matter air pollution (PM) is a risk factor for the development of atherosclerosis. Whether PM-induced lung and systemic inflammation is involved in this process is not clear. We hypothesized that PM exposure causes lung and systemic inflammation, which in turn leads to vascular endothelial dysfunction, a key step in the initiation and progression of atherosclerosis. New Zealand White rabbits were exposed for 5 days (acute, total dose 8 mg) and 4 wk (chronic, total dose 16 mg) to either PM smaller than 10 mum (PM(10)) or saline intratracheally. Lung inflammation was quantified by morphometry; systemic inflammation was assessed by white blood cell and platelet counts and serum interleukin (IL)-6, nitric oxide, and endothelin levels. Endothelial dysfunction was assessed by vascular response to acetylcholine (ACh) and sodium nitroprusside (SNP). PM(10) exposure increased lung macrophages (P<0.02), macrophages containing particles (P<0.001), and activated macrophages (P<0.006). PM(10) increased serum IL-6 levels in the first 2 wk of exposure (P<0.05) but not in weeks 3 or 4. PM(10) exposure reduced ACh-related relaxation of the carotid artery with both acute and chronic exposure, with no effect on SNP-induced vasodilatation. Serum IL-6 levels correlated with macrophages containing particles (P=0.043) and ACh-induced vasodilatation (P=0.014 at week 1, P=0.021 at week 2). Exposure to PM(10) caused lung and systemic inflammation that were both associated with vascular endothelial dysfunction. This suggests that PM-induced lung and systemic inflammatory responses contribute to the adverse vascular events associated with exposure to air pollution.
authors.affiliation: Division of Respiratory Medicine, University of British Columbia and James Hogg iCAPTURE Center for Cardiovascular and Pulmonary Research, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Eiji
authors.initials: E
authors.lastname: Tamagawa
authors.forename: Ni
authors.initials: N
authors.lastname: Bai
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Morimoto
authors.forename: Claire
authors.initials: C
authors.lastname: Gray
authors.forename: Tammy
authors.initials: T
authors.lastname: Mui
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.forename: Xuekui
authors.initials: X
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Xing
authors.forename: Yuexin
authors.initials: Y
authors.lastname: Li
authors.forename: Ismail
authors.initials: I
authors.lastname: Laher
authors.forename: Don D
authors.initials: DD
authors.lastname: Sin
authors.forename: S F Paul
authors.initials: SF
authors.lastname: Man
authors.forename: Stephan F
authors.initials: SF
authors.lastname: van Eeden
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016232:Endothelins / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000473:pathology; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D015850:Interleukin-6 / Q000378:metabolism; D007958:Leukocyte Count; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D052638:Particulate Matter / Q000633:toxicity*; D010976:Platelet Count; D011014:Pneumonia / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011817:Rabbits; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000393:Air Pollutants; D016232:Endothelins; D015850:Interleukin-6; D052638:Particulate Matter; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine