The extracellular matrix (ECM) is a deformable dynamic structure that dictates the behavior, function and integrity of blood vessels. The composition, density, chemistry and architecture of major globular and fibrillar proteins of the matrisome regulate the mechanical properties of the vasculature (i.e., stiffness/compliance). ECM proteins are linked via integrins to a protein adhesome directly connected to the actin cytoskeleton and various downstream signaling pathways that enable the cells to respond to external stimuli in a coordinated manner and maintain optimal tissue stiffness. However, cardiovascular risk factors such as diabetes, dyslipidemia, hypertension, ischemia and aging compromise the mechanical balance of the vascular wall. Stiffening of large blood vessels is associated with well-known qualitative and quantitative changes of fibrillar and fibrous macromolecules of the vascular matrisome. However, the mechanical properties of the thin-walled microvasculature are essentially defined by components of the subendothelial matrix. Cellular communication network (CCN) 1 and 2 proteins (aka Cyr61 and CTGF, respectively) of the CCN protein family localize in and act on the pericellular matrix of microvessels and constitute primary candidate markers and regulators of microvascular compliance. CCN1 and CCN2 bind various integrin and non-integrin receptors and initiate signaling pathways that regulate connective tissue remodeling and response to injury, the associated mechanoresponse of vascular cells, and the subsequent inflammatory response. The CCN1 and CCN2 genes are themselves responsive to mechanical stimuli in vascular cells, wherein mechanotransduction signaling converges into the common Rho GTPase pathway, which promotes actomyosin-based contractility and cellular stiffening. However, CCN1 and CCN2 each exhibit unique functional attributes in these processes. A better understanding of their synergistic or antagonistic effects on the maintenance (or loss) of microvascular compliance in physiological and pathological situations will assist more broadly based studies of their functional properties and translational value.

中文翻译：

---

被困在“ Rho”和困难的地方之间：CCN1 / CYR61和CCN2 / CTGF是微血管僵硬的仲裁者吗？

细胞外基质（ECM）是可变形的动态结构，决定了血管的行为，功能和完整性。基质的主要球状和原纤维蛋白的组成，密度，化学和结构调节脉管系统的机械性能（即刚度/顺应性）。ECM蛋白通过整联蛋白与直接连接至肌动蛋白细胞骨架的蛋白脂质体和各种下游信号通路相连，这些信号通路使细胞能够以协调的方式响应外部刺激并保持最佳的组织硬度。但是，诸如糖尿病，血脂异常，高血压，局部缺血和衰老等心血管危险因素会损害血管壁的机械平衡。大血管的硬化与血管基质的原纤维和纤维大分子的定性和定量变化有关。然而，薄壁微脉管系统的机械性质基本上由内皮下基质的组分定义。CCN蛋白家族的细胞通讯网络（CCN）1和2蛋白（分别为Cyr61和CTGF）位于微血管的周细胞基质中并对其起作用，并构成微血管顺应性的主要候选标记和调节剂。CCN1和CCN2结合各种整合素和非整合素受体，并启动调节结缔组织重塑和对损伤的反应，相关的血管细胞机械反应以及随后的炎症反应的信号传导途径。CCN1和CCN2基因本身对血管细胞中的机械刺激作出反应，其中机械转导信号汇聚到常见的Rho GTPase途径中，从而促进基于肌动球蛋白的收缩力和细胞硬化。但是，CCN1和CCN2在这些过程中均显示出独特的功能属性。更好地了解它们在生理和病理情况下对维持或减少微血管顺应性的协同或拮抗作用，将有助于对其功能特性和翻译价值进行更广泛的研究。在这些过程中，CCN1和CCN2各自具有独特的功能属性。更好地了解它们在生理和病理情况下对维持或减少微血管顺应性的协同或拮抗作用，将有助于对其功能特性和翻译价值进行更广泛的研究。在这些过程中，CCN1和CCN2各自具有独特的功能属性。更好地了解它们在生理和病理情况下对维持或减少微血管顺应性的协同或拮抗作用，将有助于对其功能特性和翻译价值进行更广泛的研究。