Endothelial glycocalyx degradation during sepsis: Causes and consequences.
Endothelial glycocalyx degradation during sepsis: Causes and consequences.
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DOI：
10.1016/j.mbplus.2021.100094
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发表时间：
2021-12
影响因子：
--
通讯作者：
Hippensteel JA
中科院分区：
文献类型：
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作者：
Sullivan RC;Rockstrom MD;Schmidt EP;Hippensteel JA
内皮糖萼是一种普遍存在的血管内结构，对血管稳态至关重要。在脓毒症期间，糖萼通过多种冗余脱落酶的集体作用被降解，其调控仍然是积极研究的重点。糖萼脓毒性丢失既会造成局部血管损伤（导致急性呼吸窘迫综合征和急性肾损伤），也会导致循环糖胺聚糖碎片的全身性后果（导致认知功能障碍）。脓毒症期间糖萼降解可能受到临床可改变因素的影响，这表明有机会进行治疗干预以减轻脓毒症的终末器官后果。糖萼是内皮细胞上普遍存在的结构，延伸到血管腔内。它富含蛋白聚糖，这些蛋白聚糖是附着在糖胺聚糖硫酸肝素、硫酸软骨素、硫酸皮聚糖、硫酸角蛋白和透明质酸上的蛋白质。在健康和疾病中，内皮糖萼是血管通透性、炎症、凝血和循环强直的中枢调节剂。脓毒症是一种常见于住院患者的危及生命的综合征，在脓毒症期间，内皮糖萼被降解，这是其许多临床表现的重要原因。在这篇综述中，我们讨论了脓毒性内皮糖萼破坏的内在联系机制：糖胺聚糖降解和蛋白聚糖裂解。然后，我们研究了局部内皮糖萼损失对几个器官系统的影响以及脱落的糖萼成分的系统性后果。最后，我们探讨临床相关的不可改变和可改变的因素，加剧或防止内皮糖萼脱落败血症。
The endothelial glycocalyx is a ubiquitous intravascular structure essential for vascular homeostasis. During sepsis, the glycocalyx is degraded via the collective action of a variety of redundant sheddases, the regulation of which remains the focus of active investigation. Septic loss of the glycocalyx imparts both local vascular injury (leading to acute respiratory distress syndrome and acute kidney injury) as well as the systemic consequences of circulating glycosaminoglycan fragments (leading to cognitive dysfunction). Glycocalyx degradation during sepsis is potentially shaped by clinically-modifiable factors, suggesting opportunities for therapeutic intervention to mitigate the end-organ consequences of sepsis. The glycocalyx is a ubiquitous structure found on endothelial cells that extends into the vascular lumen. It is enriched in proteoglycans, which are proteins attached to the glycosaminoglycans heparan sulfate, chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid. In health and disease, the endothelial glycocalyx is a central regulator of vascular permeability, inflammation, coagulation, and circulatory tonicity. During sepsis, a life-threatening syndrome seen commonly in hospitalized patients, the endothelial glycocalyx is degraded, significantly contributing to its many clinical manifestations. In this review we discuss the intrinsically linked mechanisms responsible for septic endothelial glycocalyx destruction: glycosaminoglycan degradation and proteoglycan cleavage. We then examine the consequences of local endothelial glycocalyx loss to several organ systems and the systemic consequences of shed glycocalyx constituents. Last, we explore clinically relevant non-modifiable and modifiable factors that exacerbate or protect against endothelial glycocalyx shedding during sepsis.