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Mohamed SA, Sievers HH, Hanke T, et al. Pathway analysis of differentially expressed genes in patients with acute aortic dissection. Biomark Insights. 2009;4:81-90doi: 10.4137/bmi.s2530.
Mohamed, S. A., Sievers, H. H., Hanke, T., Richardt, D., Schmidtke, C., Charitos, E. I., Belge, G., & Bullerdiek, J. (2009). Pathway analysis of differentially expressed genes in patients with acute aortic dissection. Biomarker insights, 481-90. https://doi.org/10.4137/bmi.s2530
Mohamed, Salah A, et al. "Pathway analysis of differentially expressed genes in patients with acute aortic dissection." Biomarker insights vol. 4 (2009): 81-90. doi: https://doi.org/10.4137/bmi.s2530
Mohamed SA, Sievers HH, Hanke T, Richardt D, Schmidtke C, Charitos EI, Belge G, Bullerdiek J. Pathway analysis of differentially expressed genes in patients with acute aortic dissection. Biomark Insights. 2009 May 06;4:81-90. doi: 10.4137/bmi.s2530. PMID: 19652764; PMCID: PMC2716678.
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Biomark Insights. 2009 May 06;4:81-90. doi: 10.4137/bmi.s2530.

Pathway analysis of differentially expressed genes in patients with acute aortic dissection.

Biomarker insights

Salah A Mohamed, Hans H Sievers, Thorsten Hanke, Doreen Richardt, Claudia Schmidtke, Efstratios I Charitos, Gazanfer Belge, Joern Bullerdiek

Affiliations

  1. Department of Cardiac Surgery, University Clinic of Schleswig-Holstein, Campus Luebeck, Luebeck, Germany.

PMID: 19652764 PMCID: PMC2716678 DOI: 10.4137/bmi.s2530

Abstract

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.

MATERIALS AND 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.

Keywords: acute aortic dissection; marfan syndrome; microarrays; pathway analysis

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