Localised micro-mechanical stiffening in the ageing aorta |
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Authors: | Graham Helen K Akhtar Riaz Kridiotis Constantinos Derby Brian Kundu Tribikram Trafford Andrew W Sherratt Michael J |
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Institution: | a Manchester Academic Health Sciences Centre, School of Biomedicine, The University of Manchester, Manchester, M13 9PT, UK b School of Materials, The University of Manchester, Manchester, M1 7HS, UK c Department of Civil Engineering and Engineering Mechanics, University of Arizona, Tucson, AZ 85721, USA |
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Abstract: | Age-related loss of tissue elasticity is a common cause of human morbidity and arteriosclerosis (vascular stiffening) is associated with the development of both fatal strokes and heart failure. However, in the absence of appropriate micro-mechanical testing methodologies, multiple structural remodelling events have been proposed as the cause of arteriosclerosis. Therefore, using a model of ageing in female sheep aorta (young: <18 months, old: >8 years) we: (i) quantified age-related macro-mechanical stiffness, (ii) localised in situ micro-metre scale changes in acoustic wave speed (a measure of tissue stiffness) and (iii) characterised collagen and elastic fibre remodelling. With age, there was an increase in both macro-mechanical stiffness and mean microscopic wave speed (and hence stiffness; young wave speed: 1701 ± 1 m s−1, old wave speed: 1710 ± 1 m s−1, p < 0.001) which was localized to collagen fibril-rich regions located between large elastic lamellae. These micro-mechanical changes were associated with increases in both collagen and elastic fibre content (collagen tissue area, young: 31 ± 2%, old: 40 ± 4%, p < 0.05; elastic fibre tissue area, young: 55 ± 3%, old: 69 ± 4%, p < 0.001). Localised collagen fibrosis may therefore play a key role in mediating age-related arteriosclerosis. Furthermore, high frequency scanning acoustic microscopy is capable of co-localising micro-mechanical and micro-structural changes in ageing tissues. |
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Keywords: | ECM extracellular matrix VSMC vascular smooth muscle cell SAM scanning acoustic microscopy MLU medial lamellar unit STAN soft tissue analysis |
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