Abstract
Purpose. The pathogenesis of thoracic aortic aneurysms and aortic dissections remains poorly understood. Despite increasing investigation, concepts of thoracic aortic aneurysm and dissection pathogenesis still rely heavily on abdominal aortic aneurysm research. We sought to use microarray technology to delve further into molecular pathogenesis of thoracic aortic aneurysms and dissections. We hypothesized that aortic gene expression profiles would differ between ascending aneurysms and dissections.
Methods. Intraoperative samples of ascending aorta were obtained during surgical repair of ascending aortic aneurysms and acute ascending aortic dissections (
n = 2 each). Control samples of ascending aorta were obtained from two organ donors. Total RNA was extracted and combined for each group, and biotinylated cDNA probes were generated. The cDNA probes were subjected to GEArray Q series microarrays containing 192 known genes related to extracellular matrix biology, adhesion molecules, and endothelial cell biology. GEArray analysis software determined relative intensities compared to controls.
Results. Compared to control tissue, 13 genes (including Enamelysin, Homo thrombospondin2, and Fibronectin1) were increased in both aneurysms and dissections. Seventeen genes were up regulated in the aneurysm group, 26 in the dissection group. Eleven genes were decreased in the aneurysm group, 10 in the dissection group. Comparing only the dissection group with the aneurysm group, 39 genes displayed much higher expression (more than 3-fold) in dissections compared to aneurysms, including Integrin alpha 8 and CD44 antigen.
Conclusions. Aortic gene expression in ascending aneurysms and acute dissections differs significantly, suggesting that different pathological mechanisms may be involved. The data extracted from these cDNA arrays will be beneficial for selecting and investigating the roles of significantly altered genes in each disease. We are currently investigating functional roles of the differentially expressed genes in each of the aortic conditions.