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A New Murine Model of Endovascular Aortic Aneurysm Repair
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Role of complement cascade in abdominal aortic aneurysms.

Irene Hinterseher1, Robert Erdman, Larry A Donoso

  • 1Sigfried and Janet Weis Center for Research, Geisinger Health System, Danville, PA 17822-2610, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|April 16, 2011
PubMed
Summary

The complement cascade is implicated in human abdominal aortic aneurysms (AAAs). Complement genes are activated in AAA tissue, suggesting STAT5A

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Area of Science:

  • Vascular Biology
  • Immunology
  • Genetics

Background:

  • Abdominal aortic aneurysms (AAAs) are life-threatening vascular diseases with complex pathobiology.
  • The role of the complement cascade in AAA development remains incompletely understood.

Purpose of the Study:

  • To investigate the involvement of complement cascade genes in the pathobiology of human AAAs.
  • To identify potential regulatory mechanisms controlling complement gene expression in AAAs.

Main Methods:

  • Genome-wide microarray expression profiling of human AAA and control aortic tissues.
  • In silico promoter analysis to identify transcription factor binding sites.
  • Chromatin-immunoprecipitation assays to validate transcription factor binding.
  • Immunohistochemical analysis of complement component C2 expression.

Main Results:

  • 3274 genes were differentially expressed between AAA and control tissues.
  • 13 complement cascade genes showed significant differential expression in AAA.
  • Transcription factor STAT5A binding sites were enriched in the promoters of these complement genes.
  • STAT5A was confirmed to bind to the promoters of most identified complement genes.
  • Strong C2 staining was observed in AAA tissues.

Conclusions:

  • The complement cascade is activated in human AAAs, particularly via the lectin and classical pathways.
  • STAT5A likely plays a key role in the coordinated regulation of complement gene expression in AAAs.
  • These findings highlight the complement system as a potential therapeutic target for AAA treatment.