title: S100A12 expression in thoracic aortic aneurysm is associated with increased risk of dissection and perioperative complications.
abstract: OBJECTIVE
  The purpose of this study was to determine the relevance of S100A12 expression to human thoracic aortic aneurysms and type A thoracic aortic aneurysm dissection and to study mechanisms of S100A12-mediated dysfunction of aortic smooth muscle cells.
  
  
  BACKGROUND
  Transgenic expression of proinflammatory S100A12 protein in murine aortic smooth muscle causes thoracic aneurysm in genetically modified mice.
  
  
  METHODS
  Immunohistochemistry of aortic tissue (n = 50) for S100A12, myeloperoxidase, and caspase 3 was examined and S100A12-mediated pathways were studied in cultured primary aortic smooth muscle cells.
  
  
  RESULTS
  We found S100A12 protein expressed in all cases of acute thoracic aortic aneurysm dissection and in approximately 25% of clinically stable thoracic aortic aneurysm cases. S100A12 tissue expression was associated with increased length of stay in patients undergoing elective surgical repair for thoracic aortic aneurysm, despite similar preoperative risk as determined by European System for Cardiac Operative Risk Evaluation. Reduction of S100A12 expression in human aortic smooth muscle cells using small hairpin RNA attenuates gene and protein expression of many inflammatory- and apoptosis-regulating factors. Moreover, genetic ablation of the receptor for S100A12, receptor for advanced glycation end products (RAGE), in murine aortic smooth muscle cells abolished cytokine-augmented activation of caspase 3 and smooth muscle cell apoptosis in S100A12-expressing cells.
  
  
  CONCLUSIONS
  S100A12 is enriched in human thoracic aortic aneurysms and dissections. Reduction of S100A12 or genetic ablation of its cell surface receptor, the receptor for advanced glycation end products (RAGE), in aortic smooth muscle resulted in decreased activation of caspase 3 and in reduced apoptosis. By establishing a link between S100A12 expression and apoptosis of aortic smooth muscle cells, this study identifies novel S100A12 signaling pathways and indicates that S100A12 may be a useful molecular marker and possible target for treatment for human aortic diseases.
authors: Department of Medicine, University of Chicago, Chicago, IL, USA.
authors: Deepanjana
authors: D
authors: Das
authors: Joseph
authors: J
authors: Gawdzik
authors: Lisa
authors: L
authors: Dellefave-Castillo
authors: Elizabeth M
authors: EM
authors: McNally
authors: Aliya
authors: A
authors: Husain
authors: Jai
authors: J
authors: Raman
authors: Marion A
authors: MA
authors: Hofmann Bowman
mesh_terms: D000784:Aortic Dissection / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D000818:Animals; D017545:Aortic Aneurysm, Thoracic / Q000378:metabolism* / Q000473:pathology* / Q000601:surgery; D017209:Apoptosis; D002478:Cells, Cultured; D006801:Humans; D015151:Immunoblotting; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009131:Muscle, Smooth, Vascular / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D059035:Perioperative Period; D011183:Postoperative Complications / Q000209:etiology / Q000378:metabolism*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics; D012107:Research Design; D009418:S100 Proteins / Q000378:metabolism*; D000067616:S100A12 Protein; D015398:Signal Transduction; D015854:Up-Regulation; D014656:Vascular Surgical Procedures / Q000009:adverse effects
chemical_list: D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D009418:S100 Proteins; D000067616:S100A12 Protein; C090441:S100A12 protein, human