Extracellular matrix-mediated remodeling and mechanotransduction in large vessels during development and disease
Extracellular matrix-mediated remodeling and mechanotransduction in large vessels during development and disease
复制标题
发育和疾病期间大血管中细胞外基质介导的重塑和机械转导
DOI：
10.1016/j.cellsig.2021.110104
复制
发表时间：
2021
影响因子：
4.8
通讯作者：
Yokoyama Utako
中科院分区：
文献类型：
--
作者：
Yanagisawa Hiromi;Yokoyama Utako
血管细胞外基质（ECM）在胚胎发育过程中合成和分泌，促进大血管的生长和重塑。ECM和血管细胞之间的适当相互作用对于建立出生后动态循环所需的脉管系统是关键的。ECM作为结构成分，维持血管壁的完整性，同时调节细胞间信号传导，其中涉及细胞因子和生长因子。大血管中的主要ECM组分是弹性纤维，其包括弹性蛋白和微纤维。弹性蛋白主要由血管平滑肌细胞（SMC）合成，并使用微纤维作为支架来铺设和组装交联弹性蛋白。缺乏弹性蛋白导致发育缺陷，导致SMC的内皮下增殖和血管壁的向内重塑。值得注意的是，弹性纤维形成在动脉导管和脐动脉中减弱。这两条血管在胚胎发生期间起作用，并在出生后通过细胞增殖、迁移和基质积累而关闭。在动态的出生后力学环境中，大血管中的弹性纤维也作为弹性蛋白收缩单位的组成部分在适当的信号转导中起重要作用。SMC中的机械转导被破坏导致病理状况，例如表现出向外重构的主动脉瘤。这篇综述讨论了ECM的重要性，主要是弹性纤维基质，在大血管发育过程中的重塑和病理条件下。通过解剖ECM在大血管中的作用，我们的目标是提供ECM介导的信号转导的作用，可以为寻求新的靶点干预血管疾病提供基础的见解。
The vascular extracellular matrix (ECM) is synthesized and secreted during embryogenesis and facilitates the growth and remodeling of large vessels. Proper interactions between the ECM and vascular cells are pivotal for building the vasculature required for postnatal dynamic circulation. The ECM serves as a structural component by maintaining the integrity of the vessel wall while also regulating intercellular signaling, which involves cytokines and growth factors. The major ECM component in large vessels is elastic fibers, which include elastin and microfibrils. Elastin is predominantly synthesized by vascular smooth muscle cells (SMCs) and uses microfibrils as a scaffold to lay down and assemble cross-linked elastin. The absence of elastin causes developmental defects that result in the subendothelial proliferation of SMCs and inward remodeling of the vessel wall. Notably, elastic fiber formation is attenuated in the ductus arteriosus and umbilical arteries. These two vessels function during embryogenesis and close after birth via cellular proliferation, migration, and matrix accumulation. In dynamic postnatal mechano-environments, the elastic fibers in large vessels also serve an essential role in proper signal transduction as a component of elastin-contractile units. Disrupted mechanotransduction in SMCs leads to pathological conditions such as aortic aneurysms that exhibit outward remodeling. This review discusses the importance of the ECM—mainly the elastic fiber matrix—in large vessels during developmental remodeling and under pathological conditions. By dissecting the role of the ECM in large vessels, we aim to provide insights into the role of ECM-mediated signal transduction that can provide a basis for seeking new targets for intervention in vascular diseases.