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Progressive development of aberrant smooth muscle cell phenotype in abdominal aortic aneurysm disease
Riches-Suman, Kirsten Clark, E. Helliwell, R.J. Angelini, T.G. Hemmings, K.E. Bailey, M.A. Bridge, K.I. Scott, D.J.A. Porter, K.E.
Riches-Suman, Kirsten
Clark, E.
Helliwell, R.J.
Angelini, T.G.
Hemmings, K.E.
Bailey, M.A.
Bridge, K.I.
Scott, D.J.A.
Porter, K.E.
Publication Date
2018
End of Embargo
Supervisor
Rights
© 2017 S. Karger AG. This is the peer-reviewed but unedited manuscript version of the following article: Riches-Suman K, Clark E, Helliwell RJ et al (2018) Progressive development of aberrant smooth muscle cell phenotype in abdominal aortic aneurysm disease. Journal of Vascular Research. 55(1): 35-46. (DOI: 10.1159/000484088). The final, published version is available at http://www.karger.com/?doi=10.1159/000484088.
Peer-Reviewed
Yes
Open Access status
openAccess
Accepted for publication
2017-10-07
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Department
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Embargo end date
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Additional title
Abstract
Abdominal aortic aneurysm (AAA) is a silent, progressive disease with high mortality and increasing prevalence with aging. Smooth muscle cell (SMC) dysfunction contributes to gradual dilatation and eventual rupture of the aorta. Here we studied phenotypic characteristics in SMC cultured from end-stage human AAA (5cm) and cells cultured from a porcine carotid artery (PCA) model of early and end-stage aneurysm.
Human AAA-SMC presented a secretory phenotype and expressed elevated levels of differentiation marker miR-145 (2.2-fold, P<.001) and senescence marker SIRT-1 (1.3-fold, P<.05), features not recapitulated in aneurysmal PCA-SMC. Human and end-stage porcine aneurysmal cells were frequently multi-nucleated (3.9-fold, P<.001 and 1.8-fold, P<.01 respectively, versus control cells) and displayed aberrant nuclear morphology. Human AAA-SMC exhibited higher levels of the DNA damage marker H2AX (3.9-fold, P<.01 vs. control SMC). These features did not correlate with patients’ chronological age; and are therefore potential markers for pathological premature vascular aging. Early-stage PCA-SMC (control and aneurysmal) were indistinguishable from one another across all parameters.
The principal limitation of human studies is tissue availability only at end-stage disease. Refinement of a porcine bioreactor model would facilitate study of temporal modulation of SMC behaviour during aneurysm development and potentially identify therapeutic targets to limit AAA progression.
Version
Accepted manuscript
Citation
Riches-Suman K, Clark E, Helliwell RJ et al (2018) Progressive development of aberrant smooth muscle cell phenotype in abdominal aortic aneurysm disease. Journal of Vascular Research. 55(1): 35-46.
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Article