Mechanical factors direct mouse aortic remodeling during early maturation

Numerous diseases have been linked to genetic mutations that lead to reduced amounts or disorganization of arterial elastic fibres. Previous work has shown that mice with reduced amounts of elastin (Eln+/−) are able to live a normal lifespan through cardiovascular adaptations, including changes in haemodynamic stresses, arterial geometry and arterial wall mechanics. It is not known if the timeline and presence of these adaptations are consistent in other mouse models of elastic fibre disease, such as those caused by the absence of fibulin-5 expression (Fbln5−/−). Adult Fbln5−/− mice have disorganized elastic fibres, decreased arterial compliance and high blood pressure. We examined mechanical behaviour of the aorta in Fbln5−/− mice through early maturation when the elastic fibres are being assembled. We found that the physiologic circumferential stretch, stress and modulus of Fbln5−/− aorta are maintained near wild-type levels. Constitutive modelling suggests that elastin contributions to the total stress are decreased, whereas collagen contributions are increased. Understanding how collagen fibre structure and mechanics compensate for defective elastic fibres to meet the mechanical requirements of the maturing aorta may help to better understand arterial remodelling in human elastinopathies.

诸多疾病已被证实与引发动脉弹性纤维（arterial elastic fibres）数量减少或结构紊乱的基因突变相关。既往研究表明，弹性蛋白（elastin）表达量降低的Eln+/−小鼠可通过心血管适应性重塑（包括血流动力学应力改变、动脉几何形态调整及动脉壁力学特性变化）维持正常寿命。目前尚不清楚这类适应性变化的发生时序与存在状态，在其他弹性纤维疾病小鼠模型（如因纤连蛋白-5（fibulin-5）表达缺失所构建的Fbln5−/−小鼠模型）中是否一致。成年Fbln5−/−小鼠存在弹性纤维结构紊乱、动脉顺应性下降及高血压表型。本研究针对处于弹性纤维组装阶段的早期成熟Fbln5−/−小鼠，检测了其主动脉的力学行为特性。研究发现，Fbln5−/−小鼠主动脉的生理性周向拉伸、应力及弹性模量均维持在与野生型（wild-type）小鼠相近的水平。本构模型（constitutive modelling）分析显示，弹性蛋白对总应力的贡献有所降低，而胶原蛋白（collagen）的贡献则相应升高。阐明胶原蛋白纤维结构与力学特性如何代偿缺陷的弹性纤维，以满足成熟主动脉的力学需求，或有助于更深入地理解人类弹性蛋白病（elastinopathies）中的动脉重塑过程。