title: Localised micro-mechanical stiffening in the ageing aorta.
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±1ms(-1), old wave speed: 1710±1ms(-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.
authors.affiliation: Manchester Academic Health Sciences Centre, School of Biomedicine, The University of Manchester, Manchester, M13 9PT, UK.
authors.forename: Helen K
authors.initials: HK
authors.lastname: Graham
authors.forename: Riaz
authors.initials: R
authors.lastname: Akhtar
authors.forename: Constantinos
authors.initials: C
authors.lastname: Kridiotis
authors.forename: Brian
authors.initials: B
authors.lastname: Derby
authors.forename: Tribikram
authors.initials: T
authors.lastname: Kundu
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Trafford
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Sherratt
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000473:pathology / Q000503:physiopathology*; D001696:Biomechanical Phenomena; D004547:Elastic Tissue / Q000473:pathology / Q000503:physiopathology; D004548:Elasticity / Q000502:physiology; D005109:Extracellular Matrix / Q000473:pathology / Q000502:physiology; D005260:Female; D033401:Microscopy, Acoustic; D012756:Sheep; D059289:Vascular Stiffness / Q000502:physiology*