Manchester Academic Health Sciences Centre, School of Biomedicine, The University of Manchester, Manchester, M13 9PT, UK.
Mech Ageing Dev. 2011 Oct;132(10):459-67. doi: 10.1016/j.mad.2011.07.003. Epub 2011 Jul 12.
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.
随着年龄的增长,组织弹性的丧失是人类发病的一个常见原因,动脉硬化(血管变硬)与致命性中风和心力衰竭的发展都有关联。然而,由于缺乏适当的微观机械测试方法,多种结构重塑事件被认为是动脉硬化的原因。因此,我们使用雌性绵羊主动脉的衰老模型(年轻:<18 个月,年老:>8 岁):(i)量化了与年龄相关的宏观机械硬度,(ii)局部原位微米级声速变化(组织硬度的一种衡量标准),以及(iii)描述了胶原蛋白和弹性纤维重塑。随着年龄的增长,宏观机械硬度和平均微观波速(因此是硬度;年轻波速:1701±1ms(-1),老年波速:1710±1ms(-1),p<0.001)均增加,这局限于位于大弹性板之间富含胶原蛋白纤维的区域。这些微观机械变化与胶原蛋白和弹性纤维含量的增加有关(胶原蛋白组织面积,年轻:31±2%,年老:40±4%,p<0.05;弹性纤维组织面积,年轻:55±3%,年老:69±4%,p<0.001)。因此,局部的胶原蛋白纤维化可能在介导与年龄相关的动脉硬化中起着关键作用。此外,高频扫描声学显微镜能够将老化组织中的微观力学和微观结构变化进行共定位。