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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Rene Schramm
  • Frank Appel
  • Manfred Reinacher
  • Hans-Joachim Schaefers
  • Benjamin Bierbach
  • Jan Slotta
  • Henrik Thorlacius
  • Michael D. Menger
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Rheumatology and Autoimmunity

Keywords

  • Atherosclerosis, Ischemia/reperfusion, GI inflammation, In vivo, inflammation, Intravital microscopy
Original languageEnglish
Pages (from-to)555-567
JournalInflammation Research
Volume60
Issue number6
Publication statusPublished - 2011
Publication categoryResearch
Peer-reviewedYes