Abstract
BackgroundWe compared gene expression profiles in acutely dissected aorta with those in normal control aorta.Materials and methodsAscending aorta specimen from patients with an acute Stanford A-dissection were taken during surgery and compared with those from normal ascending aorta from multiorgan donors using the BD Atlas™ Human1.2 Array I, BD Atlas™ Human Cardiovascular Array and the Affymetrix HG-U133A GeneChip®. For analysis only genes with strong signals of more than 70 percent of the mean signal of all spots on the array were accepted as being expressed. Quantitative real-time polymerase chain reaction (RT-PCR) was used to confirm regulation of expression of a subset of 24 genes known to be involved in aortic structure and function.ResultsAccording to our definition expression profiling of aorta tissue specimens revealed an expression of 19.1% to 23.5% of the genes listed on the arrays. Of those 15.7% to 28.9% were differently expressed in dissected and control aorta specimens. Several genes that encode for extracellular matrix components such as collagen IV α2 and -α5, collagen VI α3, collagen XIV α1, collagen XVIII α1 and elastin were down-regulated in aortic dissection, whereas levels of matrix metalloproteinases-11, -14 and -19 were increased. Some genes coding for cell to cell adhesion, cell to matrix signaling (e.g., polycystin1 and -2), cytoskeleton, as well as several myofibrillar genes (e.g., α-actinin, tropomyosin, gelsolin) were found to be down-regulated. Not surprisingly, some genes associated with chronic inflammation such as interleukin -2, -6 and -8, were up-regulated in dissection.ConclusionOur results demonstrate the complexity of the dissecting process on a molecular level. Genes coding for the integrity and strength of the aortic wall were down-regulated whereas components of inflammatory response were up-regulated. Altered patterns of gene expression indicate a pre-existing structural failure, which is probably a consequence of insufficient remodeling of the aortic wall resulting in further aortic dissection.
Highlights
We compared gene expression profiles in acutely dissected aorta with those in normal control aorta
Unpaired t-test BD AtlasTM human1.2 array According to our definition 229 of 1,185 genes (19.3%) were expressed
Partial least squares discriminant analysis (PLS-DA) We evaluated the discriminative ability of PLS-DA questioning for small gene sets to separate control and dissected aorta samples
Summary
We compared gene expression profiles in acutely dissected aorta with those in normal control aorta. Aortic dissection is a life threatening disease developing without any warning Modern diagnostic methods, such as computed or magnetic resonance tomography, are able to show an aortic wall hematoma at the acute onset of the disease. This hematoma develops to aortic wall dissection over time. It is notable that some of the dissection patients resembled Marfan patients in some aspects and demonstrated for example joint hypermobility or skin abnormalities [11]. Based on these observations the question arises: "Does an unknown connective tissue disorder cause a predisposition for aortic dissection?"
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