Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction

Abstract

BackgroundDisruption of the endothelial glycocalyx contributes to acute lung injury in experimental sepsis but has not been well studied in humans. To study glycocalyx degradation in sepsis-induced ARDS, we measured plasma levels of syndecan-1, a marker for glycocalyx degradation.MethodsThe present study is a retrospective observational study of 262 ventilated medical ICU patients at risk of ARDS due to severe sepsis and APACHE II ≥ 25. Plasma syndecan-1 was measured at study enrollment. Primary analysis focused on the association between syndecan-1 levels and the development of ARDS, other organ dysfunction (Brussels criteria), or in-hospital mortality.ResultsOverall, 135 (52%) patients developed ARDS. In patients with non-pulmonary sepsis, syndecan-1 levels were associated with ARDS (p = 0.05). Regardless of etiology of sepsis, higher syndecan-1 levels were associated with hepatic (p < 0.001), renal (p = 0.003), coagulation (p = 0.001), and circulatory (p = 0.02) failure as well as in-hospital mortality (p = 0.001), and there was a significant association between syndecan-1 levels and the number of vasopressors required in the first 24 h (p < 0.001). In addition, elevated syndecan levels were independently predictive of mortality in multivariable logistic regression adjusted for age and APACHE II score (odds ratio 1.85 per log increase in syndecan-1, 95% CI 1.056–3.241, p = 0.03).ConclusionThe extent of endothelial glycocalyx degradation is associated with non-pulmonary organ dysfunction in subjects with sepsis and is associated with ARDS but only in the subgroup with non-pulmonary sepsis. Measurement of syndecan-1 levels in sepsis patients might be useful for identifying patients at high risk of organ dysfunction and mortality as well as those who could benefit from therapies targeted at protecting or restoring the glycocalyx.

Metastatic cancer cell attachment to endothelium is promoted by endothelial glycocalyx sialic acid degradation

“…With the highest dose of 3,645 mU/mL, we noticed an ~50% decrease in both the coverage and thickness of WGA‐labeled GCX. This reduction in coverage and thickness matches pathological conditions, such as sepsis and ischemia/reperfusion and some cancers, in the degree of GCX degradation …”

The Emerging Role of Vitamin C as a Treatment for Sepsis

“…Endothelial function HDIVC decreases circulating thrombomodulin, an endothelial membrane protein receptor for thrombin that converts thrombin to an anticoagulant capable of activating protein C [95]. Decreases plasma Syndecan-1 levels, a by-product of endothelial glycocalyx shedding [96][97][98][99][100][101][102][103][104][105][106][107][108].…”

Integrating molecular pathogenesis and clinical translation in sepsis-induced acute respiratory distress syndrome

“…Thus, in contrast with direct lung injury, pathways downstream of endothelial injury (discussed below) may be disproportionately activated following indirect lung injury. This concept is supported by the observation that biomarkers related to endothelial dysfunction (e.g., angiopoietin-1) are elevated in ARDS patients with indirect lung injury, compared with those with direct lung injury (28,34).…”