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主动脉的弹性纤维和生物力学:来自小鼠研究的见解。

Elastic fibers and biomechanics of the aorta: Insights from mouse studies.

机构信息

Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tsukuba 305-8577, Japan.

Department of Mechanical Engineering and Materials Science, Washington University at St. Louis, St. Louis, MO, USA.

出版信息

Matrix Biol. 2020 Jan;85-86:160-172. doi: 10.1016/j.matbio.2019.03.001. Epub 2019 Mar 15.

Abstract

Elastic fibers are major components of the extracellular matrix (ECM) in the aorta and support a life-long cycling of stretch and recoil. Elastic fibers are formed from mid-gestation throughout early postnatal development and the synthesis is regulated at multiple steps, including coacervation, deposition, cross-linking, and assembly of insoluble elastin onto microfibril scaffolds. To date, more than 30 molecules have been shown to associate with elastic fibers and some of them play a critical role in the formation and maintenance of elastic fibers in vivo. Because the aorta is subjected to high pressure from the left ventricle, elasticity of the aorta provides the Windkessel effect and maintains stable blood flow to distal organs throughout the cardiac cycle. Disruption of elastic fibers due to congenital defects, inflammation, or aging dramatically reduces aortic elasticity and affects overall vessel mechanics. Another important component in the aorta is the vascular smooth muscle cells (SMCs). Elastic fibers and SMCs alternate to create a highly organized medial layer within the aortic wall. The physical connections between elastic fibers and SMCs form the elastin-contractile units and maintain cytoskeletal organization and proper responses of SMCs to mechanical strain. In this review, we revisit the components of elastic fibers and their roles in elastogenesis and how a loss of each component affects biomechanics of the aorta. Finally, we discuss the significance of elastin-contractile units in the maintenance of SMC function based on knowledge obtained from mouse models of human disease.

摘要

弹性纤维是主动脉细胞外基质(ECM)的主要成分,支持拉伸和回弹的终身循环。弹性纤维从中孕期到出生后早期形成,其合成受到多个步骤的调控,包括凝聚、沉积、交联和不溶性弹性蛋白组装到微纤维支架上。迄今为止,已经有 30 多种分子被证明与弹性纤维有关,其中一些在弹性纤维的形成和体内维持中起着关键作用。由于主动脉受到左心室的高压作用,主动脉的弹性提供了血流缓冲作用,在整个心动周期内维持向远端器官稳定的血流。由于先天性缺陷、炎症或衰老导致的弹性纤维破坏,会显著降低主动脉的弹性,影响整个血管的力学性能。主动脉的另一个重要组成部分是血管平滑肌细胞(SMCs)。弹性纤维和 SMC 交替排列,在主动脉壁内形成高度有序的中层。弹性纤维和 SMC 之间的物理连接形成弹性蛋白收缩单位,维持细胞骨架组织和 SMC 对机械应变的适当反应。在这篇综述中,我们回顾了弹性纤维的组成及其在弹性生成中的作用,以及每个组成部分的缺失如何影响主动脉的生物力学。最后,我们根据从人类疾病的小鼠模型中获得的知识,讨论了弹性蛋白收缩单位在维持 SMC 功能方面的意义。

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