Biomechanical activation: An emerging paradigm in endothelial adhesion biology
Biomechanical activation: An emerging paradigm in endothelial adhesion biology
复制标题
DOI：
10.1172/jci119346
复制
发表时间：
1997-04-15
影响因子：
15.9
通讯作者：
Topper, JN
中科院分区：
文献类型：
--
作者：
Gimbrone, MA;Nagel, T;Topper, JN
内皮细胞是心血管系统的单细胞层，其粘附特性是其生物学和病理学的核心。在健康的情况下，管腔内皮表面为血液的细胞和大分子成分提供了一个相对非粘附性、非血栓形成性的容器。位于细胞-细胞连接处的特异性粘附分子控制跨内皮渗透性和白细胞从血液进入身体组织空间的运动。沿着其基底面，由跨膜整联蛋白和相关的细胞内蛋白组成的粘着斑复合物将细胞外基质与细胞骨架元件物理连接，为血管衬里提供稳定性和可塑性。在疾病中，这些不同的粘附相互作用可以经历戏剧性的变化。正如本展望系列文章所强调的那样，内皮粘附病理学的分子生物学分析导致了新分子家族（例如，选择素）的发现，以及对它们相互作用的更动态的评价（例如，白细胞-内皮粘附级联）。这些知识大大增加了我们对血管生物学的基本理解，以及临床重要过程的病理生理学，如急性和慢性炎症，动脉粥样硬化，血管生成，血管损伤和修复以及发育畸形。在某些情况下，这些见解为合理设计有前途的心血管疾病新疗法提供了基础。现代血管生物学的中心前提是内皮衬里是动态可变的界面，局部响应于源自循环血液和/或邻近细胞和组织的各种刺激，因此可以积极参与脉管系统（1）的给定区域的生理适应或病理生理功能障碍。从目的论的角度来看，内皮似乎非常适合发挥这种功能，因为它在血液和组织之间具有独特的解剖位置，并且能够产生令人印象深刻的生物效应物（例如，
The adhesive properties of the endothelium, the single-cellthick lining of the cardiovascular system, are central to its biology and pathobiology. In health, the luminal endothelial surface provides a relatively nonadhesive, nonthrombogenic container for the cellular and macromolecular constituents of the blood. Specialized adhesive molecules localized at the lateral cell–cell junctions control transendothelial permeability and the movement of leukocytes from the blood into the tissue spaces of the body. Along its basal aspect, focal adhesion complexes, consisting of transmembrane integrins and associated intracellular proteins, physically link the extracellular matrix to cytoskeletal elements, providing both stability and plasticity to the vascular lining. In disease, these various adhesive interactions can undergo dramatic changes. As is highlighted by the articles in this Perspectives Series, the molecular biological analysis of endothelial adhesion pathobiology has led to the discovery of novel families of molecules (eg, the selectins), as well as a more dynamic appreciation of their mutual interactions (eg, the leukocyte–endothelial adhesion cascade). This knowledge has added much to our basic understanding of vascular biology, as well as the pathophysiology of clinically important processes, such as acute and chronic inflammation, atherosclerosis, angiogenesis, vascular injury and repair, and developmental malformations. In certain instances, these insights have provided the basis for the rational design of promising new therapeutics for cardiovascular disease.A central premise of modern vascular biology is that the endothelial lining is a dynamically mutable interface, locally responsive to various stimuli originating from the circulating blood and/or neighboring cells and tissues, and thus can actively participate in the physiological adaptation or pathophysiological dysfunction of a given region of the vasculature (1). From a teleological standpoint, the endothelium appears ideally suited to function in this capacity, given its unique anatomical position between blood and tissues, and its ability to generate an impressive repertoire of biological effectors,(eg,