Heterogeneous histomorphology, yet homogeneous vascular smooth muscle cell dedifferentiation, characterize human aneurysm disease

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Albert Busch - , University Hospital of Würzburg (Author)
  • Elena Hartmann - , University Hospital of Würzburg (Author)
  • Caroline Grimm - , University Hospital of Würzburg (Author)
  • Süleyman Ergün - , University Hospital of Würzburg (Author)
  • Ralph Kickuth - , University Hospital of Würzburg (Author)
  • Christoph Otto - , University Hospital of Würzburg (Author)
  • Richard Kellersmann - , University Hospital of Würzburg (Author)
  • Udo Lorenz - , University Hospital of Würzburg (Author)

Abstract

OBJECTIVE: 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.

METHODS: 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.

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.

CONCLUSIONS: 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.

Details

Original languageEnglish
Pages (from-to)1553-1564.e6
JournalJournal of vascular surgery
Volume66
Issue number5
Publication statusPublished - Nov 2017
Peer-reviewedYes
Externally publishedYes

External IDs

Scopus 84992109811

Keywords

Sustainable Development Goals

Keywords

  • Aneurysm/diagnostic imaging, Angiogenic Proteins/analysis, Aorta, Abdominal/chemistry, Aortic Aneurysm, Abdominal/diagnostic imaging, Aortography/methods, Biomarkers/analysis, Cell Dedifferentiation, Computed Tomography Angiography, Dilatation, Pathologic, Extracellular Matrix/chemistry, Extracellular Matrix Proteins/analysis, Humans, Inflammation/diagnostic imaging, Inflammation Mediators/analysis, Kruppel-Like Factor 4, Kruppel-Like Transcription Factors/analysis, Muscle, Smooth, Vascular/chemistry, Myocytes, Smooth Muscle/chemistry, Phenotype, Popliteal Artery/chemistry, Transforming Growth Factor beta/analysis, Vascular Remodeling