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Abstract：
The glycocalyx attached to the apical surface of vascular endothelial cells is a rich network of proteoglycans, glycosaminoglycans, and glycoproteins with instrumental roles in vascular homeostasis. Given their molecular complexity and ability to interact with the intra- and extracellular environment, heparan sulfate proteoglycans uniquely contribute to the glycocalyx\'s role in regulating endothelial permeability, mechanosignaling, and ligand recognition by cognate cell surface receptors. Much attention has recently been devoted to the enzymatic shedding of heparan sulfate proteoglycans from the endothelial glycocalyx and its impact on vascular function. However, other molecular modifications to heparan sulfate proteoglycans are possible and may have equal or complementary clinical significance. In this narrative review, we focus on putative mechanisms driving non-proteolytic changes in heparan sulfate proteoglycan expression and alterations in the sulfation of heparan sulfate side chains within the endothelial glycocalyx. We then discuss how these specific changes to the endothelial glycocalyx impact endothelial cell function and highlight therapeutic strategies to target or potentially reverse these pathologic changes.
摘要：
附着在血管内皮细胞顶端表面的糖萼是一个丰富的蛋白聚糖网络，糖胺聚糖，和糖蛋白在血管稳态中具有重要作用。鉴于它们的分子复杂性和与细胞内和细胞外环境相互作用的能力，硫酸乙酰肝素蛋白聚糖在调节内皮通透性方面的作用是独特的，机械信号，和同源细胞表面受体的配体识别。最近，人们对硫酸乙酰肝素蛋白聚糖从内皮糖萼中的酶促脱落及其对血管功能的影响进行了广泛关注。然而,硫酸乙酰肝素蛋白聚糖的其他分子修饰是可能的,可能具有相同或互补的临床意义.在这篇叙述性评论中，我们关注的是驱动硫酸乙酰肝素蛋白聚糖表达的非蛋白水解变化和内皮糖萼内硫酸乙酰肝素侧链硫酸化变化的推定机制.然后，我们讨论了内皮细胞糖萼的这些特定变化如何影响内皮细胞功能，并强调了靶向或潜在逆转这些病理变化的治疗策略。
