title: Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms.
abstract: BACKGROUND
  Since aortic diameter is the most -significant risk factor for rupture, we sought to identify stress-dependent changes in gene expression to illuminate novel molecular processes in aneurysm rupture.
  
  
  METHODS
  We constructed finite element maps of abdominal computerized tomography scans (CTs) of seven abdominal aortic aneurysm (AAA) patients to map wall stress. Paired biopsies from high- and low-stress areas were collected at surgery using vascular landmarks as coordinates. Differential gene expression was evaluated by Illumina Array analysis, using the whole genome DNA-mediated, annealing, selection, extension, and ligation (DASL) gene chip (n = 3 paired samples).
  
  
  RESULTS
  The sole significant candidate from this analysis, Lamin A/C, was validated at the protein level, using western blotting. Lamin A/C expression in the inferior mesenteric vein (IMV) of AAA patients was compared to a control group and in aortic smooth muscle cells in culture in response to physiological pulsatile stretch. -Areas of high wall stress (n = 7) correlate to those -regions which have the thinnest walls [778 µm (585-1120 µm)] in comparison to areas of lowest wall stress [1620 µm (962-2919 µm)]. Induced expression of Lamin A/C -correlated with areas of high wall stress from AAAs but was not significantly induced in the IMV from AAA patients compared to controls (n = 16). Stress-induced expression of Lamin A/C was mimicked by exposing aortic smooth muscle cells to prolonged pulsatile stretch.
  
  
  CONCLUSIONS
  Lamin A/C protein is specifically increased in areas of high wall stress in AAA from patients, but is not increased on other vascular beds of aneurysm patients, suggesting that its elevation may be a compensatory response to the pathobiology leading to aneurysms.
authors.affiliation: Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK.
authors.forename: Amir
authors.initials: A
authors.lastname: Malkawi
authors.affiliation: Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK.
authors.forename: Grisha
authors.initials: G
authors.lastname: Pirianov
authors.affiliation: Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK.
authors.forename: Evelyn
authors.initials: E
authors.lastname: Torsney
authors.affiliation: Centre for Cardiovascular & Metabolic Research, York Hull Medical School, Hull, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Chetter
authors.affiliation: Department of Cardiovascular Surgery, University Hospital of Liege, Liege, Belgium.
authors.forename: Natzi
authors.initials: N
authors.lastname: Sakalihasan
authors.affiliation: Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK.
authors.forename: Ian M
authors.initials: IM
authors.lastname: Loftus
authors.affiliation: Department of Vascular Surgery, University Hospital Southampton, Southampton, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Nordon
authors.affiliation: Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK.
authors.forename: Christopher
authors.initials: C
authors.lastname: Huggins
authors.affiliation: Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK.
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Charolidi
authors.affiliation: Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK.
authors.forename: Matt
authors.initials: M
authors.lastname: Thompson
authors.affiliation: Department of Chemical Engineering, Imperial College London, London, UK.
authors.forename: Xie Yun
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK.
authors.forename: Gillian W
authors.initials: GW
authors.lastname: Cockerill
keywords: Aging; Nuclear lamina; Smooth muscle cells; Stretch