Patient specific wall stress analysis demonstrated that wall stress was higher in AAA's at risk of rupture. Furthermore, there is a correlation between sites of rupture and high wall stress regions. We set out to investigate the gene expression in regions of high and low wall stress to identify the role of wall stress in the pathogenesis of AAA Methods Finite element analysis (PEA, ADINA R&D Inc., Watertown, USA) was performed on patients with AAA scheduled for open repair. Regions of high and low wall stress were identified from the obtained patient specific wall stress map. Coordinates of regions of high and low stress were mapped on a three-dimensional reconstruction of each aneurysm which included major visceral branches as reference points to aid in intra-operative localization. High and low stress regions were marked intra-operatively on the aneurysm surface according to their distance from the reference points and full-thickness biopsies were obtained. RNA was extracted (RNeasy Fibrous Tissue RNA Extraction Kit, Qiagen, UK) and whole genome profiling was performed (Illurnina HumanRef-8 v3.0 Expression BeadChips). Protein expression was determined by Western blotting. Results PEA was performed on 11 patients. Paired samples were obtained from high and low wall stress regions. AAA wall was found to be thinner in regions exposed to high wall stress. There was over-expression of LMNA (Larnin AlC) in high wall stress regions. Over-expression of lamin AlC was also demonstrated on Western blotting. Conclusion Our results identify novel pre-rupture changes in AAA's in regions exposed to high stress. This is the first study to identify a role for lamin AlC in AAA pathogenesis. Over expression of lamin A/C in high wall stress regions highlights the role of cytoskeletal and nuclear mechanics, mechanotransduction and apoptotic transcriptional pathways in AAA development and rupture.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:558352 |
| Date | January 2012 |
| Creators | Malkawi, Amir H. |
| Publisher | St George's, University of London |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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