Pathway analysis of differentially expressed genes in patients with acute aortic dissection.
BACKGROUND
Acute aortic dissection (AAD) is a life-threatening condition with high mortality and a relatively unclarified pathophysiological mechanism. Although differentially expressed genes in AAD have been recognized, interactions between these genes remain poorly defined. This study was conducted to gain a better understanding of the molecular mechanisms underlying AAD and to support the future development of a clinical test for monitoring patients at high risk.


METHODS
Aortic tissue was collected from 19 patients with AAD (mean age 61.7 +/- 13.1 years), and from eight other patients (mean age 32.9 +/- 12.2 years) who carried the mutated gene for Marfan syndrome (MS). Six patients (mean age 56.7 +/- 12.3 years) served as the control group. The PIQOR(TM) Immunology microarray with 1076 probes in quadruplicates was utilized; the differentially expressed genes were analysed in a MedScan search using Pathway Assist software. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and protein analysis were performed.


RESULTS
Interactions of MS fibrillin-1 (FBN1) in the MedScan pathway analysis showed four genes, fibulin-1 (FBLN1), fibulin-2 (FBLN2), decorin (DCN) and microfibrillar associated protein 5 (MFAP5), which were differentially expressed in all tissue from AAD. The validation of these genes by qRT-PCR revealed a minimum of three-fold downregulation of FBLN1 (0.5 +/- 0.4 vs. 6.1 +/- 2.3 fold, p = 0.003) and of DCN (2.5 +/- 1.0 vs. 8.5 +/- 4.7 fold, p = 0.04) in AAD compared to MS and control samples.


CONCLUSIONS
Downregulation of fibrillin-1 (FBN1) may weaken extracellular components in the aorta and/or interfer with the transmission of cellular signals and eventually cause AAD. Additional research on these four identified genes can be a starting point to develop a diagnostic tool.
Mohamed
Salah A
SA
Department of Cardiac Surgery, University Clinic of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.
Sievers
Hans H
HH
Hanke
Thorsten
T
Richardt
Doreen
D
Schmidtke
Claudia
C
Charitos
Efstratios I
EI
Belge
Gazanfer
G
Bullerdiek
Joern
J