title: Apolipoprotein E-deficient mice are susceptible to the development of acute lung injury.
abstract: BACKGROUND
  Apolipoprotein E (apoE) has been shown to play a pivotal role in the development of cardiovascular disease, attributable to its function in lipid trafficking and immune modulating properties; however, its role in modulating inflammation in the setting of acute lung injury (ALI) is unknown.
  
  
  OBJECTIVE
  To determine whether apoE-deficient mice (apoE-/-) are more susceptible to ALI compared to wild-type (WT) animals.
  
  
  METHODS
  Two independent models of ALI were employed. Firstly, WT and apoE-/- mice were randomized to acid aspiration (50 μl of 0.1 N hydrochloric acid) followed by 4 h of mechanical ventilation. Secondly, WT and apoE-/- mice were randomized to 72 h of hyperoxia exposure or room air. Thereafter, the intrinsic responses of WT and apoE-/- mice were assessed using the isolated perfused mouse lung (IPML) setup. Finally, based on elevated levels of oxidized low-density lipoprotein (oxLDL) in apoE-/-, the effect of oxLDL on lung endothelial permeability and inflammation was assessed.
  
  
  RESULTS
  In both in vivo models, apoE-/- mice demonstrated greater increases in lung lavage protein levels, neutrophil counts, and cytokine expression (p < 0.05) compared to WT mice. Experiments utilizing the IPML setup demonstrated no differences in intrinsic lung responses to injury between apoE-/- and WT mice, suggesting the presence of a circulating factor as being responsible for the in vivo observations. Finally, the exposure of lung endothelial cells to oxLDL resulted in increased monolayer permeability and IL-6 release compared to native (nonoxidized) LDL.
  
  
  CONCLUSIONS
  Our findings demonstrate a susceptibility of apoE-/- animals to ALI that may occur, in part, due to elevated levels of oxLDL.
authors.affiliation: Lawson Health Research Institute, London, Ont., Canada.
authors.forename: Cory M
authors.initials: CM
authors.lastname: Yamashita
authors.forename: Michael B
authors.initials: MB
authors.lastname: Fessler
authors.forename: Lakshman
authors.initials: L
authors.lastname: Vasanthamohan
authors.forename: Joanne
authors.initials: J
authors.lastname: Lac
authors.forename: Jennifer
authors.initials: J
authors.lastname: Madenspacher
authors.forename: Lynda
authors.initials: L
authors.lastname: McCaig
authors.forename: Lijuan
authors.initials: L
authors.lastname: Yao
authors.forename: Lefeng
authors.initials: L
authors.lastname: Wang
authors.forename: Valeria
authors.initials: V
authors.lastname: Puntorieri
authors.forename: Sanjay
authors.initials: S
authors.lastname: Mehta
authors.forename: Jim F
authors.initials: JF
authors.lastname: Lewis
authors.forename: Ruud A W
authors.initials: RA
authors.lastname: Veldhuizen
mesh_terms: D055371:Acute Lung Injury / Q000209:etiology / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics*; D004195:Disease Models, Animal; D020022:Genetic Predisposition to Disease; D006851:Hydrochloric Acid / Q000633:toxicity; D007249:Inflammation; D015850:Interleukin-6 / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism* / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010539:Permeability / Q000187:drug effects; D012121:Respiration, Artificial / Q000009:adverse effects; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D015850:Interleukin-6; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein; D006851:Hydrochloric Acid