| Autor: |
Yamashita, Cory M., Fessler, Michael B., Vasanthamohan, Lakshman, Lac, Joanne, Madenspacher, Jennifer, McCaig, Lynda, Yao, Lijuan, Wang, Lefeng, Puntorieri, Valeria, Mehta, Sanjay, Lewis, Jim F., Veldhuizen, Ruud A.W. |
| Předmět: |
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| Zdroj: |
Respiration; Apr2014, Vol. 87 Issue 5, p416-427, 12p, 1 Chart, 6 Graphs |
| Abstrakt: |
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. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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