Whole genome-expression profiling reveals a role for immune and inflammatory response in abdominal aortic aneurysm rupture

Eur J Vasc Endovasc Surg. 2009 Mar;37(3):305-10. doi: 10.1016/j.ejvs.2008.11.017. Epub 2008 Dec 25.

Abstract

Objectives: This study used the whole transcriptome approach to investigate the role of genes involved in immune and inflammatory response at the site of aneurysm rupture.

Materials and methods: Rupture site and paired anterior sac biopsies (internal control) of ruptured abdominal aortic aneurysms (AAAs) (n=10) were analysed with Affymetrix Human Genome U133A plus 2.0 microarray. Twenty-one differentially expressed genes were selected for validation using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR).

Results: A total of 139 genes (123 upregulated, 16 downregulated) at the aneurysm rupture site were differentially expressed (>2.5-fold, P<0.005). Immune and inflammatory responses (Gene Ontology Classification) were frequently associated with the differentially expressed genes. Genes with immune and inflammatory functions that were confirmed, by QRT-PCR, to be overexpressed at the aneurysm rupture site were interleukins-6 and -8 (IL-6 and -8), Selectin E (SELE), prostaglandin-endoperoxidase synthase 2 (COX2) and prokineticin 2 (PROK2). IL-6 (pro-immune) and IL-8 (pro-immune and pro-inflammatory) have previously been linked to aneurysm rupture; and SELE and COX2 (pro-inflammatory) have previous associations with aneurysm development but not rupture.

Conclusions: The differential expression of genes involved in immune and inflammatory responses was confirmed at AAA rupture site. These genes may represent novel targets for treatment of aneurysms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aortic Aneurysm, Abdominal / genetics*
  • Aortic Aneurysm, Abdominal / pathology
  • Aortic Rupture / genetics*
  • Cyclooxygenase 2 / genetics*
  • Cytokines / genetics*
  • E-Selectin / genetics*
  • Gastrointestinal Hormones / genetics*
  • Gene Expression Profiling*
  • Genome, Human
  • Humans
  • Inflammation / genetics
  • Microarray Analysis
  • Middle Aged
  • Neuropeptides / genetics*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Cytokines
  • E-Selectin
  • Gastrointestinal Hormones
  • Neuropeptides
  • PROK2 protein, human
  • RNA, Messenger
  • Cyclooxygenase 2