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


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.
Choke
E
E
St George's Vascular Institute, St George's Hospital, Blackshaw Road, Tooting, London SW17 0RE, UK.
Cockerill
G W
GW
Laing
K
K
Dawson
J
J
Wilson
W R W
WR
Loftus
I M
IM
Thompson
M M
MM
D000368:Aged; D000369:Aged, 80 and over; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics* / Q000473:pathology; D001019:Aortic Rupture / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D019040:E-Selectin / Q000235:genetics*; D005768:Gastrointestinal Hormones / Q000235:genetics*; D020869:Gene Expression Profiling; D015894:Genome, Human; D006801:Humans; D007249:Inflammation / Q000235:genetics; D046228:Microarray Analysis; D008875:Middle Aged; D009479:Neuropeptides / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D016207:Cytokines; D019040:E-Selectin; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human; D012333:RNA, Messenger; D051546:Cyclooxygenase 2