Adhesion molecules and their role in vascular disease
Adhesion molecules and their role in vascular disease
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DOI：
10.1016/s0895-7061(01)02069-6
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发表时间：
2001-06-01
影响因子：
3.2
通讯作者：
Granger, DN
中科院分区：
文献类型：
--
作者：
Krieglstein, CF;Granger, DN
各种最近发现的糖蛋白已涉及细胞-细胞相互作用，这对正常止血、免疫监视和血管壁完整性至关重要。已知这些细胞粘附分子（CAM）介导血细胞（白细胞、血小板）-内皮细胞相互作用，在某些生理（例如止血）和病理（例如炎症）条件下，这些相互作用可发生在微血管系统的所有节段中。白细胞募集的多步骤过程说明了CAM的结构和功能不同家族的协调和调节表达如何引起对炎症的高度可重复的血管反应。选择素介导初始的低亲和力白细胞-内皮细胞相互作用，表现为白细胞滚动。这种瞬时结合导致进一步的白细胞活化和随后的白细胞的牢固粘附和跨内皮迁移，这两者都是由CAM的整合素和免疫球蛋白超家族成员之间的相互作用介导的。这种CAM调节的白细胞募集过程通常导致内皮细胞功能障碍，其可表现为小动脉中内皮依赖性血管舒张受损、毛细血管中过度液体过滤和小静脉中蛋白质外渗增强。因此，CAM与多种血管疾病（例如，缺血/再灌注、动脉粥样硬化、同种异体移植物功能障碍和血管炎）有关，这些CAM的表达增强被用来解释与心血管疾病的一些风险因素（高血压、高胆固醇血症、糖尿病）相关的夸大的微血管功能障碍。单克隆抗体和基因工程小鼠已被证明是确定CAM对疾病进展的贡献的有价值的工具，并为心血管疾病的新诊断和治疗策略提供了希望。美国高血压杂志2001;14：44 S-54 S（C）2001年美国高血压杂志，有限公司。
A variety of recently discovered glycoproteins have been implicated in cell-cell interactions that are critical for normal hemostasis, immune surveillance, and vascular wall integrity. These cell adhesion molecules (CAM) are known to mediate blood cell (leukocyte, platelet)- endothelial cell interactions that can occur in all segments of the microvasculature under certain physiological (eg, hemostasis) and pathological (eg, inflammation) conditions. The multistep process of leukocyte recruitment illustrates how the coordinated and regulated expression of structurally and functionally distinct families of CAM can elicit a highly reproducible vascular response to inflammation. Selectins mediate the initial, low-affinity leukocyte- endothelial cell interaction that is manifested as leukocyte rolling. This transient binding results in further leukocyte activation and subsequent firm adhesion and transendothelial migration of leukocytes, both of which are mediated by interactions between members of the integrin and immunoglobulin superfamily of CAM. This CAM-regulated process of leukocyte recruitment often results in endothelial cell dysfunction, which can be manifested as either impaired endothelium-dependent vasorelaxation in arterioles, excess fluid filtration in capillaries, and enhanced protein extravasation in venules. Consequently, CAM have been implicated in a variety of vascular disorders (eg, ischemia/reperfusion, atherosclerosis, allograft dysfunction, and vasculitis) and an enhanced expression of these CAM has been invoked to explain the exaggerated microvascular dysfunction associated with some of the risk factors (hypertension, hypercholesterolemia, diabetes) for cardiovascular disease. Monoclonal antibodies and genitically engineered mice have proven to be valuable tools for defining the contribution of CAM to disease progression and provide hope for new diagnostic and therapeutic strategies for cardiovascular diseases. Am J Hypertens 2001;14: 44S-54S (C) 2001 American Journal of Hypertension, Ltd.