[en] 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 microm (585-1120 microm)] in comparison to areas of lowest wall stress [1620 microm (962-2919 microm)]. 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.
Disciplines :
Surgery
Author, co-author :
Malkawi, Amir
Pirianov, Grisha
Torsney, Evelyn
Chetter, Ian
Sakalihasan, Natzi ; Université de Liège > Département des sciences cliniques > Biologie pathologique des parois artérielles
Loftus, Ian M.
Nordon, Ian
Huggins, Christopher
Charolidi, Nicoletta
Thompson, Matt
Xu, Xie Yun
Cockerill, Gillian W.
Language :
English
Title :
Increased Expression of Lamin A/C Correlate with Regions of High Wall Stress in Abdominal Aortic Aneurysms.
Publication date :
2015
Journal title :
Aorta
eISSN :
2325-4637
Publisher :
Science International Corporation, Stamford, United States - Connecticut
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
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