Rupture - Transcriptional Profile

Objective

The pathophysiological features of aneurysm growth are well documented, whilst little is known about the process associated with rupture. To gain further insights into the mechanism of rupture we have compared the transcriptional profile of tissue samples collected proximal to the rupture sites with paired samples collected from the anterior sac.

Methods

Paired biopsies were obtained from the rupture site and anterior sac in 12 ruptured AAAs. Gene array profiles (Affymetrix™, HG133 Plus2™) were compared (n=3) between rupture and anterior sac from pooled RNAs from all 12 patients. Differential expression of selected candidate genes were confirmed using quantitative-real time-PCR and cellular localisation examined using immunohistochemistry.

Results

Table 1. Statistically significant differentially expressed genes (p<0.008)*

Cellular Process Gene Name Relative Expression (mean ± sd)

(Accession Nos) Rupture Anterior Sac

Apoptosis Nuclear receptor 4A2 1.77±0.098 0.277±0.039

(A1935096)

Immediate Early Response3 1.453±0.02 0.567±0.06

(NM-003897)

Inflammation E-selectin 1.91±0.062 0.069±0.035

(NM-000450)

Oncostatin M Receptor 1.353±0.010 0.567±0.083

(BC010943)

Regulated G protein S16 1.828±0.162 0.300±0.28

(BF304996)

Angiogenesis Four and a half Lim 1 0.523±0.061 1.465±0.023

(AF098518)

* Multiple testing correction: Benjamini&Hochberg applied.

Table 2. Statistically significant differentially expressed genes (p<0.01)

Cellular Process Gene Name Relative Expression (mean ± sd)

(Accession Nos)

Rupture Anterior Sac

Apoptosis GADD45G 1.780±0.68 0.707±0.002

(NM-006705)

TNF SF9 2.001±1.09 0.565±0.118

(NM-003811)

RAD21 1.375±0.377 0.957±0.002

(BC 031280)

Angiogenesis VEGF 1.541±0.23 0.532±0.07

(M27281)

PROK 2 1.923±0.25 0.271±0.06

(AF182069)

IL8 1.737±0.079 0.300±0.032

(NM-001430)

EPAS1 0.848±0.17 1.206±0.19

(NM-001430)

KDR 2.561±0.34 0.745±0.125

(U01134)

Conclusion

Our findings support our previous data (reported at this meeting) demonstrating the significance of neo-angiogenesis in aneurysmal rupture. Whilst the importance of smooth muscle cell apoptosis has previously been suggested to contribute to aneurysm degeneration, this is the first report to associate apoptosis to rupture and provide a number of potential target genes relating to the process.