Hyaluronan regulation of vascular integrity.
Hyaluronan regulation of vascular integrity.
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DOI：
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发表时间：
2011
影响因子：
1.3
通讯作者：
Frances E. Lennon;P. Singleton
中科院分区：
文献类型：
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作者：
Frances E. Lennon;P. Singleton
血管完整性或血管连续性的维持是一个基本过程，部分由内皮糖萼和细胞-细胞连接调节。内皮屏障功能缺陷是动脉粥样硬化、缺血/再灌注、肿瘤血管生成、癌症转移、糖尿病、败血症和急性肺损伤等多种疾病过程的启动因素。糖胺聚糖，透明质酸（HA），通过内皮糖萼调节、小泡蛋白富集微域调控和与内皮HA结合蛋白的相互作用，维持血管的完整性。某些疾病状态增加透明质酸酶活性和活性氧（ROS）的产生，将高分子量HA分解为低分子量片段，造成内皮糖萼损伤。此外，这些HA片段可以激活在血管疾病中上调的特异性HA结合蛋白，促进肌动蛋白细胞骨架重组和抑制内皮细胞-细胞接触。本文综述了透明质酸在血管完整性中的重要作用，以及透明质酸降解如何促进血管屏障的破坏。
Vascular integrity or the maintenance of blood vessel continuity is a fundamental process regulated, in part, by the endothelial glycocalyx and cell-cell junctions. Defects in endothelial barrier function are an initiating factor in several disease processes including atherosclerosis, ischemia/reperfusion, tumor angiogenesis, cancer metastasis, diabetes, sepsis and acute lung injury. The glycosaminoglycan, hyaluronan (HA), maintains vascular integrity through endothelial glycocalyx modulation, caveolin-enriched microdomain regulation and interaction with endothelial HA binding proteins. Certain disease states increase hyaluronidase activity and reactive oxygen species (ROS) generation which break down high molecular weight HA to low molecular weight fragments causing damage to the endothelial glycocalyx. Further, these HA fragments can activate specific HA binding proteins upregulated in vascular disease to promote actin cytoskeletal reorganization and inhibition of endothelial cell-cell contacts. This review focuses on the crucial role of HA in vascular integrity and how HA degradation promotes vascular barrier disruption.