title: Diesel exhaust inhalation induces heat shock protein 70 expression in vivo.
abstract: Exposure to urban air pollution is an independent risk factor for increased cardiovascular diseases. Heat shock protein 70 (HSP70) has been implicated in the pathogenesis of vascular dysfunction and cardiovascular diseases. This study has been designed to determine whether inhalation of urban air induces HSP70 expression in the lung and blood as well as the association of HSP70 and air pollution-induced vascular dysfunction. Apolipoprotein E (Apo-E) deficient mice were exposed to diesel exhaust (DE) either acutely (3 days, 200 or 400 µg/m(3) for 6 h/day) or chronically (7 weeks, 200 or 400 µg/m(3) for 6 h/day). HSP70 was measured in the lung using immunohistochemistry, and in the plasma by ELISA. Abdominal aorta rings were used to determine vascular functional responses. Chronic DE-exposure increased the fraction of HSP70 positive alveolar macrophages (AM) that was related to the fraction of particle-laden AM in the lung (r(2) =  0.48, p <0.01). Chronic DE-exposure increased plasma HSP70 levels and reduced blood vessel responses to phenylephrine (PE). The fraction of particle-laden HSP70 positive AM was associated with abnormal vasoconstriction responses to PE induced by DE-exposure (r(2) = 0.12, p = 0.02). Our results show that chronic inhalation of DE increases HSP70 expression in the lung and systemic circulation, and we postulate that HSP70 possibly contributes to air pollution induced vascular dysfunction and cardiovascular diseases.
authors.affiliation: The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia, St. Paul's Hospital, Vancouver, British Columbia, Canada.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kido
authors.forename: Ni
authors.initials: N
authors.lastname: Bai
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.forename: Hisashi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Anna
authors.initials: A
authors.lastname: Meredith
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Michael E
authors.initials: ME
authors.lastname: Rosenfeld
authors.forename: Stephan F
authors.initials: SF
authors.lastname: van Eeden
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001012:Aorta, Abdominal / Q000187:drug effects / Q000378:metabolism; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D001057:Apolipoproteins E / Q000172:deficiency; D002318:Cardiovascular Diseases / Q000139:chemically induced / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000097:blood; D007150:Immunohistochemistry; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D014661:Vasoconstriction / Q000187:drug effects; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D001057:Apolipoproteins E; D018840:HSP70 Heat-Shock Proteins; D001335:Vehicle Emissions