Division of Nephrology, Department of Internal Medicine, the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Division of Nephrology, Department of Internal Medicine, the Einthoven Laboratory for Vascular and Regenerative Medicine, Leiden University Medical Center, Leiden, the Netherlands.
Am J Pathol. 2020 Apr;190(4):781-790. doi: 10.1016/j.ajpath.2019.07.022. Epub 2020 Feb 6.
The endothelial glycocalyx is critically involved in vascular integrity and homeostasis, by regulating vascular permeability, regulating mechanotransduction, and reducing inflammation and coagulation. The turnover of the glycocalyx is dynamic to fine-tune these processes. This is in particular true for its main structural component, hyaluronan (HA). Degradation and shedding of the glycocalyx by enzymes, such as hyaluronidase 1 and hyaluronidase 2, are responsible for regulation of the glycocalyx thickness and hence access of circulating cells and factors to the endothelial cell membrane and its receptors. This degradation process will at the same time also allow for resynthesis and adaptive chemical modification of the glycocalyx. The (re)synthesis of HA is dependent on the availability of its sugar substrates, thus linking glycocalyx biology directly to cellular glucose metabolism. It is therefore of particular interest to consider the consequences of dysregulated cellular glucose in diabetes for glycocalyx biology and its implications for endothelial function. This review summarizes the metabolic regulation of endothelial glycocalyx HA and its potential as a therapeutic target in diabetic vascular complications.
内皮糖萼对于血管完整性和稳态至关重要，它可以调节血管通透性、机械转导，减少炎症和凝血。糖萼的更新是动态的，可以精细地调节这些过程。其主要结构成分透明质酸（HA）尤其如此。酶（如透明质酸酶 1 和透明质酸酶 2）降解和脱落糖萼，负责调节糖萼的厚度，从而使循环细胞和因子能够进入内皮细胞膜及其受体。这个降解过程同时也允许糖萼的重新合成和适应性化学修饰。HA 的（再）合成依赖于其糖底物的可用性，因此将糖萼生物学直接与细胞葡萄糖代谢联系起来。因此，考虑糖尿病中细胞葡萄糖失调对糖萼生物学及其对内皮功能的影响是非常重要的。这篇综述总结了内皮糖萼 HA 的代谢调节及其作为糖尿病血管并发症治疗靶点的潜力。
