CHEST Guidelines-Ultrastructural-Alteration-of-Pulmonary-Capillary-

Ultrastructural-Alteration-of-Pulmonary-Capillary-

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The study titled "Ultrastructural Alteration of Pulmonary Capillary Endothelial Glycocalyx During Endotoxemia" by Risa Inagawa et al., investigates the disruption of the glycocalyx in pulmonary capillary endothelium during endotoxemia, a component of sepsis leading to Acute Respiratory Distress Syndrome (ARDS). Consisting of sugar-proteins, the glycocalyx lines healthy vascular endothelium and is vital in maintaining vascular permeability, inhibiting thrombosis, and regulating leukocyte adhesion.<br /><br />The study utilized a mouse model induced with lipopolysaccharide (LPS) to simulate endotoxemia. Three-dimensional imaging techniques, including scanning and transmission electron microscopy, were used to examine the endothelial glycocalyx. In healthy mice, the glycocalyx appeared as a moss-like layer completely covering endothelial cells. However, post-LPS injection, this structure appeared severely disrupted—peeling off and coagulating.<br /><br />The study observed significant reductions in syndecan-1 levels, a component of glycocalyx, indicating its degradation. Spherical structures containing glycocalyx were noted at the endothelial surface, suggesting cellular shedding under endotoxemic conditions. The research also measured increased vascular permeability through Evans blue extravasation, confirming endothelial dysfunction.<br /><br />Results showed that the glycocalyx disruption coincided with an increase in plasma syndecan-1 levels, amid higher permeability and activated neutrophil binding—hallmarks of endothelial injury. Notably, recovery of the glycocalyx was documented within 96 hours post-LPS exposure, proposing it could spontaneously regenerate.<br /><br />The study concludes that glycocalyx degradation contributes to microvascular dysfunction in sepsis-induced ARDS. Addressing glycocalyx preservation or repair could be beneficial in managing sepsis-related complications. The findings underscore the critical role of glycocalyx in endothelial health and sepsis pathology, highlighting the potential therapeutic target to mitigate vascular leakage and organ dysfunction in septic patients.

Keywords

glycocalyx

endotoxemia

pulmonary capillary

endothelial dysfunction

ARDS

sepsis

syndecan-1

vascular permeability

lipopolysaccharide

microvascular dysfunction