Heat stress combined with lipopolysaccharide induces pulmonary microvascular endothelial cell glycocalyx inflammatory damage in vitro

Abstract

AbstractHeat 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.