Abstract
BackgroundIncreased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure. Shedding of the endothelial glycocalyx is increasingly being recognized as an important pathophysiological mechanism but at present it is unclear if glypicans contribute to this response. We hypothesized that plasma levels of glypicans (GPC) are elevated in patients with sepsis.MethodsPlasma GPC 1–6 levels were measured by ELISA in 10 patients with sepsis and 10 healthy controls as an initial screening. Plasma GPC 1, 3, and 4 were further measured in a cohort of 184 patients with a clinically confirmed infection. Patients were divided into groups of those who had sepsis and those who had an infection without organ failure. To determine whether plasma glypicans could predict the development of organ failure, patients were further subdivided to those who had organ failure at enrolment and those who developed it after enrollment. The association of plasma GPC 1, 3, and 4 with organ failure and with various markers of inflammation, disease severity, and glycocalyx shedding was investigated.ResultsIn the pilot study, only GPC 1, 3, and 4 were detectable in the plasma of sepsis patients. In the larger cohort, GPC 1, 3, and 4 levels were significantly higher (p < 0.001) in patients with sepsis than in those with infection without organ failure. GPC 1, 3, and 4 were significantly positively correlated with plasma levels of the disease severity markers C-reactive protein, lactate, procalcitonin, and heparin binding protein, and with the marker of glycocalyx degradation syndecan 1. They were significantly negatively correlated with plasma levels of the glycocalyx-protective factors apolipoprotein M and sphingosine-1-phosphate.ConclusionsWe show that GPC 1, 3, and 4 are elevated in plasma of patients with sepsis and correlate with markers of disease severity, systemic inflammation, and glycocalyx damage.
Highlights
Increased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure
GPC 1, 3, and 4 and glycocalyx shedding Because inflammatory conditions, including sepsis, are associated with massive shedding of the glycocalyx from endothelial and other cell surfaces, we examined whether GPC 1, 3, and 4 shedding may occur in conjunction with the shedding of other glycocalyx components (Table 2)
We report for the first time that glypican 1, 3, and 4 levels are elevated in the plasma of patients with sepsis compared to those with infection without organ failure
Summary
Increased vascular permeability is a key feature in the pathophysiology of sepsis and the development of organ failure. Shedding of the endothelial glycocalyx is increasingly being recognized as an important pathophysiological mechanism but at present it is unclear if glypicans contribute to this response. The breakdown of endothelial barrier function, leading to vascular leak, edema, and organ failure, is central to the pathophysiology of sepsis [2, 3]. Fisher et al Intensive Care Medicine Experimental (2019) 7:2 functions for vascular homeostasis It acts as a sensor of shear stress, it provides receptor sites for a number of signaling molecules, it maintains an antithrombotic surface, and by creating a negatively charged fiber matrix, it contributes to the barrier function of the endothelium [5,6,7]. Most endothelial proteoglycans are secreted, while syndecans and glypicans remain attached to the cell membrane [8]. The six glypicans primarily contain heparan sulfate and are attached to the phospholipids of the membrane via a glycosylphosphatidylinositol anchor [8]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call