The Endothelial Glycocalyx: New Diagnostic and Therapeutic Approaches in Sepsis

Abstract

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. The endothelial glycocalyx is one of the earliest sites involved during sepsis. This fragile layer is a complex network of cell-bound proteoglycans, glycosaminoglycan side chains, and sialoproteins lining the luminal side of endothelial cells with a thickness of about 1 to 3 μm. Sepsis-associated alterations of its structure affect endothelial permeability and result in the liberation of endogenous damage-associated molecular patterns (DAMPs). Once liberated in the circulatory system, DAMPs trigger the devastating consequences of the proinflammatory cascades in sepsis and septic shock. In this way, the injury to the glycocalyx with the consecutive release of DAMPs contributes to a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and septic cardiomyopathy. Moreover, the extent of glycocalyx degradation serves as a marker of endothelial dysfunction and sepsis severity. In this review, we highlight the crucial role of the glycocalyx in sepsis as a diagnostic tool and discuss the potential of members of the endothelial glycocalyx serving as hopeful therapeutic targets in sepsis-associated multiple organ failures.

The Measurement of the Endothelial Glycocalyx as a New Biomarker of Endothelial Derangement in Systemic Sclerosis: A Challenge for the Future

“…The modification of EG dimensions and function has been reported in sepsis, diabetes, obesity, cardiovascular disease, endstage renal disease, and hypercholesterolemia 13,14,15,16 . Few data are reported regarding SSc where the failure of the EG might significantly impair the endothelial barrier function, the capacity to inhibit coagulation and leukocyte adhesion, and also the shear stress-induced nitric oxide release, with a significant deterioration of the vascular tone control 12,17 .…”

Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling

“…Secondary to the primary cause of the malaise, the microvascular reactions to pathological challenges often result in either severe comorbidity, such as in the case of respiratory disease ( e.g. COPD and acute respiratory distress syndrome) or sepsis , where EC activation compounds primary symptoms through added oedema, permeability and positive feedback of inflammatory signals. Endothelial activation in response to disturbed flow underlies atherosclerosis, a condition also shown to result from damage to the endothelial glycocalyx , but also results in a feed‐forward loop that exacerbates the condition and fosters the establishment of further and wide‐ranging complications.…”

Neutrophil extracellular trap stabilization leads to improved outcomes in murine models of sepsis

“…In sepsis, end-organ injury involves damage to the microvasculature 32 . Therefore, we sought to determine if PF4-mediated compaction alters NETs' ability to harm the endothelium.…”