The Endothelial Glycocalyx: Physiology and Pathology in Neonates, Infants and Children

Abstract

The endothelial glycocalyx (EG) as part of the endothelial surface layer (ESL) is an important regulator of vascular function and homeostasis, including permeability, vascular tone, leukocyte recruitment and coagulation. Located at the interface between the endothelium and the blood stream, this highly fragile structure is prone to many disruptive factors such as inflammation and oxidative stress. Shedding of the EG has been described in various acute and chronic diseases characterized by endothelial dysfunction and angiopathy, such as sepsis, trauma, diabetes and cardiovascular disease. Circulating EG components including syndecan-1, hyaluronan and heparan sulfate are being evaluated in animal and clinical studies as diagnostic and prognostic markers in several pathologies, and advances in microscopic techniques have enabled in vivo assessment of the EG. While research regarding the EG in adult physiology and pathology has greatly advanced throughout the last decades, our knowledge of the development of the glycocalyx and its involvement in pathological conditions in the pediatric population is limited. Current evidence suggests that the EG is present early during fetal development and plays a critical role in vessel formation and maturation. Like in adults, EG shedding has been demonstrated in acute inflammatory conditions in infants and children and chronic diseases with childhood-onset. However, the underlying mechanisms and their contribution to disease manifestation and progression still need to be established. In the future, the glycocalyx might serve as a marker to identify pediatric patients at risk for vascular sequelae and as a potential target for early interventions.

The endothelial glycocalyx in critical illness: A pediatric perspective

“…Puchwein-Schwepcke et al [2] have nicely summarized the literature available characterizing EG injury in children undergoing congenital heart surgery. As with adults [205] , [206] , exposure to CPB results in increased circulating levels of SDC1, heparan sulfate, and hyaluronan in children [207] , [208] , [209] , [210] , corresponding to decreased EG thickness on videomicroscopy [211] .…”

“…Biomarker evaluation and SDF videomicroscopy have been most commonly used to characterize EG damage in children [2] . However, performing even these limited assessments can be difficult to perform and interpret in critically ill children.…”

“…Relative to adults, very little is known about the EG in pediatric critical illness. A recent review has nicely summarized the current state of the literature characterizing glycocalyx damage in pediatric diseases [2] . Arguably, each of the 14 studies reported in that review are, or can be, related to pediatric critical illness.…”

Topical Reappraisal of Molecular Pharmacological Approaches to Endothelial Dysfunction in Diabetes Mellitus Angiopathy

“…Diabetic endothelial dysfunction is thought to be manifested by an early increase in vascular permeability. The fiber-matrix theory of microvascular permeability holds that the ability of the capillary wall to act as a molecular sieve is a feature conferred by the endothelial glycocalyx [ 33 ].…”

The Endothelial Glycocalyx and Neonatal Sepsis

“…The first approach measures the levels of eGC-detached components in plasma/serum and urine, such as syndecan-1 (SDC-1), hyaluronan (HA), heparan sulphate (HS), and heparan sulphate chondroitin (CS). The second approach uses the video microscopic assessment of the eGC in the microcirculation vessels [20].…”