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CC BY 4.0 · Aorta (Stamford) 2015; 03(05): 152-161
DOI: 10.12945/j.aorta.2015.14.069
Original Research Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms

Amir Malkawi   †
1   Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK
,
Grisha Pirianov   †
1   Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK
,
Evelyn Torsney
1   Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK
,
Ian Chetter
2   Centre for Cardiovascular & Metabolic Research, York Hull Medical School, Hull, UK
,
Natzi Sakalihasan
3   Department of Cardiovascular Surgery, University Hospital of Liege, Liege, Belgium
,
Ian M. Loftus
1   Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK
,
Ian Nordon
4   Department of Vascular Surgery, University Hospital Southampton, Southampton, UK
,
Christopher Huggins
1   Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK
,
Nicoletta Charolidi
1   Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK
,
Matt Thompson
1   Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK
,
Xie Yun Xu
5   Department of Chemical Engineering, Imperial College London, London, UK
,
Gillian W. Cockerill
1   Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, UK
› Author Affiliations
Further Information

Publication History

06 November 2014

18 May 2015

Publication Date:
24 September 2018 (online)

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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.

Materials and 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.

Conclusion: 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.

Key Words

Nuclear lamina - Stretch - Smooth muscle cells - Aging

† The following authors contributed equally to the work in this manuscript.


Supplementary Material

 

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