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

Aims: Dissections of the thoracic aorta represent despite their high mortality a least clarified entity of the arterial diseases. The aim of this study was to find out if in dissected aortic tissues there are significant similarities in their gene expression pattern and compare these to known Marfan syndrome (MS). In addition, it was of interest to look for genes involved in the inflammatory processes.

Methods: Aortic tissues were collected during surgery from 19 patients with acute aortic dissection (AAD, mean age 61.7±13.1 years) and from 8 patients with MS (mean age 32.9±12.2 years). The mRNA from all those tissues was extracted and hybridized competitively on the PIQORTM Immunology array with 1070 probes in quadruplicates. In order to get an idea about the biological meaning of the differential expression of the common up- and down regulated genes, those genes were subjected to biological pathway analysis.

Results: 88 genes, which showed at least 2-fold up- or down-regulation were generated and clustered according to their biological annotations. A number of matrix metalloproteases were differentially expressed in AAD tissues. The expression levels of 6 collagens were reduced, and 6 chemokines were strongly downregulated. CCL2 and IL6 were upregulated, interactions with MS FBN1 considered 6 genes (DCN, FBLN2, MMP 19, S100A12, MFAP5 and FBLN1). RT-PCR validation of these genes presented in all ADD samples a least 3-fold upregulation of FBLN2, 16-fold upregulation of MMP19 and 75-fold of S100A12.

Conclusions: Upregulation of FBLN2, MMP19 and S100A12 genes may contributed to AAD diseases.