Endothelial Glycocalyx Degradation in Critical Illness and Injury

Abstract

The endothelial glycocalyx is a gel-like layer on the luminal side of blood vessels that is composed of glycosaminoglycans and the proteins that tether them to the plasma membrane. Interest in its properties and function has grown, particularly in the last decade, as its importance to endothelial barrier function has come to light. Endothelial glycocalyx studies have revealed that many critical illnesses result in its degradation or removal, contributing to endothelial dysfunction and barrier break-down. Loss of the endothelial glycocalyx facilitates the direct access of immune cells and deleterious agents (e.g., proteases and reactive oxygen species) to the endothelium, that can then further endothelial cell injury and dysfunction leading to complications such as edema, and thrombosis. Here, we briefly describe the endothelial glycocalyx and the primary components thought to be directly responsible for its degradation. We review recent literature relevant to glycocalyx damage in several critical illnesses (sepsis, COVID-19, trauma and diabetes) that share inflammation as a common denominator with actions by several common agents (hyaluronidases, proteases, reactive oxygen species, etc.). Finally, we briefly cover strategies and therapies that show promise in protecting or helping to rebuild the endothelial glycocalyx such as steroids, protease inhibitors, anticoagulants and resuscitation strategies.

The association between hypoalbuminemia and microcirculation, endothelium and glycocalyx disorders in children with sepsis.

“…The Wilcoxon test was used to evaluate the differences in non-normally distributed biomarkers from dependent groups. Confounding factors were controlled for in the design, using the exclusion criteria to restrict patients who might have other reasons to explain the endothelial glycocalyx damage previously described in the literature, like ketoacidosis or trauma [5,8,11]. Confounding (especially disease severity assessed by the PIM-2 scale, malnutrition, the use of vasoactive medications and the use of 20% albumin infusions) was also controlled for in the statistical analysis plan by carrying out multivariate analysis using logistic regression.…”

Treating COVID-19: Targeting the Host Response, Not the Virus

“…The pathophysiology of COVID-19 has been extensively reviewed [ 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 ], especially in relation to endothelial dysfunction [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 ]. The acute disease is also characterized by extensive modification of innate and adaptive immunity, increased inflammatory cytokines, abnormal interferon responses and immunothrombosis ( Figure 1 ).…”

Recent advances in critical care: Part II

“…Albumin physiologically binds to the glycocalyx and prevents its shedding, thereby ensuring vascular integrity and normal capillary permeability. [ 6 , 9 ]…”