Gene expression analysis of non-syndromic ascending aortic aneurysms

The non-syndromic ascending aortic aneurysm is a complex and common disease. Little is known on gene expression and its regulation in aneurysms. The media coat is principally involved in the disease. Aim of this study is to identify gene expression differences between aneurysmal and normal ascending aortic media coats. A total of 41 aneurysmal aortic samples (cases) and 22 aortic samples without aneurysm (controls), has been collected from patients undergoing aneurysmectomy and heart transplantation, respectively. Gene expression analyses on media coats RNA have been conducted by whole genome microarrays, which detect a total of 21,329 human genes, Real Time PCR, and microRNA microarrays. Results from whole genome microarrays performed on 3 cases and a pool of 10 controls indicated a total of 17 differentially expressed genes, among which Period homolog 2 (PER2), involved in circadian rhythm, was upexpressed, and Decorin (DCN), involved in remodeling, was downexpressed. The analysis of 4 pool of 3 cases versus a pool of 15 controls confirmed PER2 up-expression. Presently, we validated by Real Time PCR PER2 up-expression and DCN down-expression in aneurysms. Expression study of a comparison of transcriptomic analysis with proteomic data confirmed up-regulation of 6 genes out of 15 investigated, including NOTCH1 , involved in vascular development. Expression study of selected genes of NF-kB cascade evidenced a proinflammatory status of aneurysmal subjects with bicuspid aortic valve compared to the normal and to tricuspid aortic valve aneurysmal subjects. Initial microRNA microarray analysis indicates that mir-133, related to NO signaling, may be down-regulated in aneurysms. In conclusion, genes mainly involved in inflammation and remodeling have been identified with this study. Further expression analyses will better indicate pathways involved in thoracic aortic aneurysms development.