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

J Vasc Surg. 2017 Nov;66(5):1553-1564.e6. doi: 10.1016/j.jvs.2016.07.129. Epub 2016 Oct 5.

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.

MeSH terms

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

Substances

  • Angiogenic Proteins
  • Biomarkers
  • Extracellular Matrix Proteins
  • Inflammation Mediators
  • KLF4 protein, human
  • Kruppel-Like Factor 4
  • Kruppel-Like Transcription Factors
  • Transforming Growth Factor beta