title: Inflammation-related induction of absent in melanoma 2 (AIM2) in vascular cells and atherosclerotic lesions suggests a role in vascular pathogenesis.
abstract: BACKGROUND
  Absent in melanoma (AIM2) was recently identified to act as a cytosolic DNA sensor in innate immunity. Considering the role of chronic inflammation in atherosclerosis, we hypothesized that AIM2 may act as a damage signal that is activated in response to cellular stress likewise in vascular cells of larger arteries. We thus addressed AIM2 expression in healthy arterial wall and in different vascular lesions. In addition, AIM2 expression was characterized in cultured human aortic endothelial cells (HAoECs), smooth muscle cells (HAoSMCs), and T/G-HA-vascular smooth muscle cells (VSMCs) in response to different stimuli.
  
  
  METHODS
  Carotid and aortic lesions from patients who underwent surgery and normal arterial specimens were analyzed by immunohistochemistry for AIM2 expression. Cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs were stimulated in vitro with proinflammatory cytokines (tumor necrosis factor-α, interferon-γ) or poly(dA:dT) and analyzed for AIM2 transcript and protein expression.
  
  
  RESULTS
  AIM2 was detected in ECs of the intima and vasa vasorum of normal carotid artery and aorta. Moreover, AIM2 was moderately expressed in VSMCs of normal media and intima layers, as well as in VSMCs of atherosclerotic lesions. Increased AIM2 expression was detected around the necrotic core of atherosclerotic carotid lesions and in the vasa vasorum neovasculature of aortic aneurysms. Subsequent in vitro analysis identified an endogenous AIM2 expression in cultured HAoECs, HAoSMCs, and T/G-HA-VSMCs that was markedly increased upon treatment of the cells with tumor necrosis factor-α, interferon-γ, or cytosolic DNA.
  
  
  CONCLUSIONS
  ECs and VSMC are able to respond to inflammatory signals by upregulation of AIM2 expression, indicating a role of AIM2 in vascular pathogenesis.
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Maani
authors.initials: M
authors.lastname: Hakimi
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peters
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Becker
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Dittmar
authors.initials: D
authors.lastname: Böckler
authors.affiliation: Department of Vascular and Endovascular Surgery, University Hospital Heidelberg, Heidelberg, Germany. Electronic address: susanne.dihlmann@med.uni-heidelberg.de.
authors.forename: Susanne
authors.initials: S
authors.lastname: Dihlmann
mesh_terms: D001018:Aortic Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050197:Atherosclerosis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002340:Carotid Artery Diseases / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002460:Cell Line; D004268:DNA-Binding Proteins; D042783:Endothelial Cells / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000276:immunology / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000276:immunology / Q000378:metabolism*; D009336:Necrosis; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D058226:Plaque, Atherosclerotic; D011067:Poly dA-dT / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C410167:AIM2 protein, human; D004268:DNA-Binding Proteins; C573415:IFNG protein, human; D018836:Inflammation Mediators; D009687:Nuclear Proteins; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D011067:Poly dA-dT; D007371:Interferon-gamma