Kim Jungsil, Staiculescu Marius Catalin, Cocciolone Austin J, Yanagisawa Hiromi, Mecham Robert P, Wagenseil Jessica E
Dept. of Mechanical Engineering and Materials Science, Washington University, St. Louis, MO, United States.
Life Science Center of Tsukuba Advance Research Alliance, University of Tsukuba, Japan.
J Biomech. 2017 Aug 16;61:199-207. doi: 10.1016/j.jbiomech.2017.07.011. Epub 2017 Jul 25.
In the large arteries, it is believed that elastin provides the resistance to stretch at low pressure, while collagen provides the resistance to stretch at high pressure. It is also thought that elastin is responsible for the low energy loss observed with cyclic loading. These tenets are supported through experiments that alter component amounts through protease digestion, vessel remodeling, normal growth, or in different artery types. Genetic engineering provides the opportunity to revisit these tenets through the loss of expression of specific wall components. We used newborn mice lacking elastin (Eln) or two key proteins (lysyl oxidase, Lox, or fibulin-4, Fbln4) that are necessary for the assembly of mechanically-functional elastic fibers to investigate the contributions of elastic fibers to large artery mechanics. We determined component content and organization and quantified the nonlinear and viscoelastic mechanical behavior of Eln, Lox, and Fbln4 ascending aorta and their respective controls. We confirmed that the lack of elastin, fibulin-4, or lysyl oxidase leads to absent or highly fragmented elastic fibers in the aortic wall and a 56-97% decrease in crosslinked elastin amounts. We found that the resistance to stretch at low pressure is decreased only in Eln aorta, confirming the role of elastin in the nonlinear mechanical behavior of the aortic wall. Dissipated energy with cyclic loading and unloading is increased 53-387% in Eln, Lox, and Fbln4 aorta, indicating that not only elastin, but properly assembled and crosslinked elastic fibers, are necessary for low energy loss in the aorta.
在大动脉中，人们认为弹性蛋白在低压下提供抗拉伸阻力，而胶原蛋白在高压下提供抗拉伸阻力。人们还认为弹性蛋白是循环加载时观察到的低能量损失的原因。这些原则通过一些实验得到了支持，这些实验通过蛋白酶消化、血管重塑、正常生长或在不同动脉类型中改变成分含量。基因工程提供了通过缺失特定壁成分的表达来重新审视这些原则的机会。我们使用缺乏弹性蛋白（Eln）或两种对机械功能弹性纤维组装至关重要的关键蛋白质（赖氨酰氧化酶，Lox，或纤连蛋白-4，Fbln4）的新生小鼠，来研究弹性纤维对大动脉力学的贡献。我们确定了成分含量和组织，并量化了Eln、Lox和Fbln4升主动脉及其各自对照的非线性和粘弹性力学行为。我们证实，缺乏弹性蛋白、纤连蛋白-4或赖氨酰氧化酶会导致主动脉壁中弹性纤维缺失或高度碎片化，交联弹性蛋白含量减少56-97%。我们发现，仅在Eln主动脉中，低压下的抗拉伸阻力降低，这证实了弹性蛋白在主动脉壁非线性力学行为中的作用。在Eln、Lox和Fbln4主动脉中，循环加载和卸载时耗散的能量增加了53-387%，这表明不仅弹性蛋白，而且正确组装和交联的弹性纤维对于主动脉中的低能量损失都是必要的。
