In:
Respiration, S. Karger AG, Vol. 87, No. 5 ( 2014), p. 416-427
Abstract:
〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Objective: 〈 /i 〉 〈 /b 〉 To determine whether apoE-deficient mice (apoE-/-) are more susceptible to ALI compared to wild-type (WT) animals. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 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. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our findings demonstrate a susceptibility of apoE-/- animals to ALI that may occur, in part, due to elevated levels of oxLDL.
Type of Medium:
Online Resource
ISSN:
0025-7931
,
1423-0356
Language:
English
Publisher:
S. Karger AG
Publication Date:
2014
detail.hit.zdb_id:
1464419-8
