中暑是一种危及生命的疾病，具有很高的死亡率和并发症。内皮糖萼 (EGCX) 对于维持内皮细胞结构和功能以及防止炎症细胞粘附至关重要。炎症和凝血失衡背后的潜在关系仍然难以捉摸。此外，EGCX 在中暑引起的器官损伤中的作用仍不清楚。因此，本研究旨在阐明EGCX是否会加重人肺微血管内皮细胞（HPMEC）的凋亡、炎症和氧化损伤。采用热应激和脂多糖（LPS）构建体外模型，研究糖萼结构和功能的变化，以及硫酸乙酰肝素蛋白聚糖（HSPG）、syndecan-1（SDC-1）、硫酸乙酰肝素（HS）、肿瘤水平的变化。坏死因子-α (TNF-α)、白细胞介素 (IL)-6、血管性血友病因子 (vWF)、内皮素-1 (ET-1)、occludin、E-选择素、血管细胞粘附分子-1 (VCAM-1)和活性氧（ROS）。在这里，我们发现热应激和 LPS 破坏了 EGCX 结构，激活了 EGCX 降解，并引发了 HPMEC 的氧化损伤和细胞凋亡。热应激和LPS的刺激降低了HSPG的表达，增加了培养物上清液中SDC-1和HS的水平，促进了促炎细胞因子（TNF-α和IL-6）和凝血因子（vWF和ET-1）的产生和释放。 ）在 HPMEC 中。此外，E-selection、VCAM-1和ROS的表达上调，而occludin的表达下调。这些变化可能会因乙酰肝素酶而恶化，而会因普通肝素而改善。这项研究表明，EGCX 可能会导致细胞凋亡和中暑引起的凝血病，这些影响可能是由于 EGCX 脱落减少所致。© 2023 作者。约翰·威利出版的《免疫、炎症和疾病》

Heat stroke is a life-threatening disease with high mortality and complications. Endothelial glycocalyx (EGCX) is essential for maintaining endothelial cell structure and function as well as preventing the adhesion of inflammatory cells. Potential relationship that underlies the imbalance in inflammation and coagulation remains elusive. Moreover, the role of EGCX in heat stroke-induced organ injury remained unclear. Therefore, the current study aimed to illustrate if EGCX aggravates apoptosis, inflammation, and oxidative damage in human pulmonary microvascular endothelial cells (HPMEC). Heat stress and lipopolysaccharide (LPS) were employed to construct in vitro models to study the changes of glycocalyx structure and function, as well as levels of heparansulfate proteoglycan (HSPG), syndecan-1 (SDC-1), heparansulfate (HS), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, Von Willebrand factor (vWF), endothelin-1 (ET-1), occludin, E-selectin, vascular cell adhesion molecule-1 (VCAM-1), and reactive oxygen species (ROS). Here, we showed that heat stress and LPS devastated EGCX structure, activated EGCX degradation, and triggered oxidative damage and apoptosis in HPMEC. Stimulation of heat stress and LPS decreased expression of HSPG, increased levels of SDC-1 and HS in culture supernatant, promoted the production and release of proinflammation cytokines (TNF-α and IL-6,) and coagulative factors (vWF and ET-1) in HPMEC. Furthermore, Expressions of E-selection, VCAM-1, and ROS were upregulated, while that of occludin was downregulated. These changes could be deteriorated by heparanase, whereas they meliorated by unfractionated heparin. This study indicated that EGCX may contribute to apoptosis and heat stroke-induced coagulopathy, and these effects may have been due to the decrease in the shedding of EGCX.© 2023 The Authors. Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.