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Atherosclerosis aggravates ischemia/reperfusion injury in the gut and remote damage in the liver and the lung

Schramm, Rene ; Appel, Frank ; Reinacher, Manfred ; Schaefers, Hans-Joachim ; Bierbach, Benjamin ; Slotta, Jan ; Thorlacius, Henrik LU and Menger, Michael D. (2011) In Inflammation Research 60(6). p.555-567
Abstract
Objective We investigated whether mesenteric ischemia/reperfusion (I/R)-associated gut injury and remote liver and lung damage are affected by prevalent atherosclerosis. Methods Mesenteric ischemia was induced in atherosclerotic ApoE-deficient (ApoE(-/-)) and control C57BL/6 mice by clamping the superior mesenteric artery for 30 min. Mesenteric microcirculatory dysfunction and leukocytic inflammation were studied in the terminal ileum by intravital fluorescence microscopy (IVM). Histological analyses included quantitative assessment of parenchymal injury in the terminal ileum, liver and lung. Results In the gut, IVM of the terminal ileum revealed aggravated postischemic microcirculatory dysfunction and absence of reactive hyperemia-induced... (More)
Objective We investigated whether mesenteric ischemia/reperfusion (I/R)-associated gut injury and remote liver and lung damage are affected by prevalent atherosclerosis. Methods Mesenteric ischemia was induced in atherosclerotic ApoE-deficient (ApoE(-/-)) and control C57BL/6 mice by clamping the superior mesenteric artery for 30 min. Mesenteric microcirculatory dysfunction and leukocytic inflammation were studied in the terminal ileum by intravital fluorescence microscopy (IVM). Histological analyses included quantitative assessment of parenchymal injury in the terminal ileum, liver and lung. Results In the gut, IVM of the terminal ileum revealed aggravated postischemic microcirculatory dysfunction and absence of reactive hyperemia-induced vasodilation in atherosclerotic mice compared to controls. In addition, leukocyte-endothelial cell adhesive interactions, i.e. rolling and firm adhesion, were significantly increased in atherosclerotic animals. This was associated with enhanced mucosal tissue damage in ApoE(-/-) mice. Moreover, mesenteric I/R-provoked remote parenchymal injury in the liver was found to be significantly aggravated in atherosclerotic mice. This was accompanied by enhanced neutrophilic lung inflammation in ApoE(-/-) mice. Conclusion Prevalent generalized atherosclerosis not only aggravates splanchnic microcirculatory dysfunction and leukocytic inflammation in response to mesenteric I/R, but also exacerbates mucosal tissue damage and remote injury in the liver and the lung. (Less)
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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Atherosclerosis, Ischemia/reperfusion, GI inflammation, In vivo, inflammation, Intravital microscopy
in
Inflammation Research
volume
60
issue
6
pages
555 - 567
publisher
Birkhäuser Verlag
external identifiers
  • wos:000290679000007
  • scopus:79956193948
  • pmid:21222016
ISSN
1420-908X
DOI
10.1007/s00011-010-0304-3
language
English
LU publication?
yes
id
6435eea5-4583-43e6-96a5-d0fc451deefc (old id 1986333)
date added to LUP
2016-04-01 10:14:52
date last changed
2022-01-25 21:16:46
@article{6435eea5-4583-43e6-96a5-d0fc451deefc,
  abstract     = {{Objective We investigated whether mesenteric ischemia/reperfusion (I/R)-associated gut injury and remote liver and lung damage are affected by prevalent atherosclerosis. Methods Mesenteric ischemia was induced in atherosclerotic ApoE-deficient (ApoE(-/-)) and control C57BL/6 mice by clamping the superior mesenteric artery for 30 min. Mesenteric microcirculatory dysfunction and leukocytic inflammation were studied in the terminal ileum by intravital fluorescence microscopy (IVM). Histological analyses included quantitative assessment of parenchymal injury in the terminal ileum, liver and lung. Results In the gut, IVM of the terminal ileum revealed aggravated postischemic microcirculatory dysfunction and absence of reactive hyperemia-induced vasodilation in atherosclerotic mice compared to controls. In addition, leukocyte-endothelial cell adhesive interactions, i.e. rolling and firm adhesion, were significantly increased in atherosclerotic animals. This was associated with enhanced mucosal tissue damage in ApoE(-/-) mice. Moreover, mesenteric I/R-provoked remote parenchymal injury in the liver was found to be significantly aggravated in atherosclerotic mice. This was accompanied by enhanced neutrophilic lung inflammation in ApoE(-/-) mice. Conclusion Prevalent generalized atherosclerosis not only aggravates splanchnic microcirculatory dysfunction and leukocytic inflammation in response to mesenteric I/R, but also exacerbates mucosal tissue damage and remote injury in the liver and the lung.}},
  author       = {{Schramm, Rene and Appel, Frank and Reinacher, Manfred and Schaefers, Hans-Joachim and Bierbach, Benjamin and Slotta, Jan and Thorlacius, Henrik and Menger, Michael D.}},
  issn         = {{1420-908X}},
  keywords     = {{Atherosclerosis; Ischemia/reperfusion; GI inflammation; In vivo; inflammation; Intravital microscopy}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{555--567}},
  publisher    = {{Birkhäuser Verlag}},
  series       = {{Inflammation Research}},
  title        = {{Atherosclerosis aggravates ischemia/reperfusion injury in the gut and remote damage in the liver and the lung}},
  url          = {{http://dx.doi.org/10.1007/s00011-010-0304-3}},
  doi          = {{10.1007/s00011-010-0304-3}},
  volume       = {{60}},
  year         = {{2011}},
}