title: Heterogeneous histomorphology, yet homogeneous vascular smooth muscle cell dedifferentiation, characterize human aneurysm disease.
abstract: Abdominal aortic aneurysm (AAA) is a frequent, potentially life-threatening, disease that can only be treated by surgical means such as open surgery or endovascular repair. No alternative treatment is currently available, and despite expanding knowledge about the pathomechanism, clinical trials on medical aneurysm abrogation have led to inconclusive results. The heterogeneity of human AAA based on histologic examination is thereby generally neglected. In this study we aimed to further elucidate the role of these differences in aneurysm disease.
  
  
  
  Tissue samples from AAA and popliteal artery aneurysm patients were examined by histomorphologic analysis, immunohistochemistry, Western blot, and polymerase chain reaction. The results were correlated with clinical data such as aneurysm diameter and laboratory results.
  
  
  
  The morphology of human AAA vessel wall probes varies tremendously based on the grade of inflammation. This correlates with increasing intima/media thickness and upregulation of the vascular endothelial growth factor cascade but not with any clinical parameter or the aneurysm diameter. The phenotypic switch of vascular smooth muscle cells occurred regardless of the inflammatory state and expressional changes of the transcription factors Kruppel-like factor-4 and transforming growth factor-β lead to differential protein localization in aneurysmal compared with control arteries. These changes were in similar manner also observed in samples from popliteal artery aneurysms, which, however, showed a more homogenous phenotype.
  
  
  
  Heterogeneity of AAA vessel walls based on inflammatory morphology does not correlate with AAA diameter yet harbors specific implications for basic research and possible aneurysm detection.
authors.affiliation: Department of General, Visceral, Vascular & Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany. Electronic address: busch_a2@ukw.de.
authors.forename: Albert
authors.initials: A
authors.lastname: Busch
authors.affiliation: Institute of Pathology and Comprehensive Cancer Center (CCC) Mainfranken, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Elena
authors.initials: E
authors.lastname: Hartmann
authors.affiliation: Department of General, Visceral, Vascular & Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Grimm
authors.affiliation: Institute of Anatomy and Cell Biology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Süleyman
authors.initials: S
authors.lastname: Ergün
authors.affiliation: Department of Diagnostic and Interventional Radiology, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Ralph
authors.initials: R
authors.lastname: Kickuth
authors.affiliation: Department of General, Visceral, Vascular & Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Otto
authors.affiliation: Department of General, Visceral, Vascular & Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Richard
authors.initials: R
authors.lastname: Kellersmann
authors.affiliation: Department of General, Visceral, Vascular & Pediatric Surgery, University Hospital Würzburg, Würzburg, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Lorenz
mesh_terms: D000783:Aneurysm / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D042501:Angiogenic Proteins / Q000032:analysis; D001012:Aorta, Abdominal / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D001027:Aortography / Q000379:methods; D015415:Biomarkers / Q000032:analysis; D054337:Cell Dedifferentiation; D000072226:Computed Tomography Angiography; D004108:Dilatation, Pathologic; D005109:Extracellular Matrix / Q000737:chemistry / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D006801:Humans; D007249:Inflammation / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000032:analysis; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000473:pathology*; D032389:Myocytes, Smooth Muscle / Q000737:chemistry / Q000473:pathology*; D010641:Phenotype; D011150:Popliteal Artery / Q000737:chemistry / Q000000981:diagnostic imaging / Q000473:pathology; D016212:Transforming Growth Factor beta / Q000032:analysis; D066253:Vascular Remodeling
chemical_list: D042501:Angiogenic Proteins; D015415:Biomarkers; D016326:Extracellular Matrix Proteins; D018836:Inflammation Mediators; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D051741:Kruppel-Like Transcription Factors; D016212:Transforming Growth Factor beta