Endothelial glycocalyx as a potential theriapeutic target in organ injuries

Abstract

Objective: The endothelial glycocalyx (eGC) is a dynamic and multicomponent layer of macromolecules found at the surface of vascular endothelium, which is largely underappreciated. It has recently been recognized that eGC is a major regulator of endothelial function and may have therapeutic value in organ injuries. This study aimed to explore the role of the eGC in various pathologic and physiologic conditions, by reviewing the basic research findings pertaining to the detection of the eGC and its clinical significance. We also explored different pharmacologic agents used to protect and rebuild the eGC. Data sources: An in-depth search was performed in the PubMed database, focusing on research published after 2003 with keywords including eGC, permeability, glycocalyx and injuries, and glycocalyx protection. Study selection: Several authoritative reviews and original studies were identified and reviewed to summarize the characteristics of the eGC under physiologic and pathologic conditions as well as the detection and protection of the eGC. Results: The eGC degradation is closely associated with pathophysiologic changes such as vascular permeability, edema formation, mechanotransduction, and clotting cascade, together with neutrophil and platelet adhesion in diverse injury and disease states including inflammation (sepsis and trauma), ischemia-reperfusion injury, shock, hypervolemia, hypertension, hyperglycemia, and high Na + as well as diabetes and atherosclerosis. Therapeutic strategies for protecting and rebuilding the eGC should be explored through experimental test and clinical verifications. Conclusions: Disturbance of the eGC usually occurs at early stages of various clinical pathophysiologies which can be partly prevented and reversed by protecting and restoring the eGC. The eGC seems to be a promising diagnostic biomarker and therapeutic target in clinical settings.

Can Endothelial Glycocalyx Be a Major Morphological Substrate in Pre-Eclampsia?

“…A promising approach from the standpoint of etiotropic therapy aimed to protect eGC, is the use of anticoagulant drugs: heparin (unfractionated heparin (UFH), low-molecular-weight heparin (LMWH)) and heparinoids (sulodexide) [99]. Heparin is very similar to heparan sulfate, which is the main structural component of eGC.…”

“…Heparinoids are heparin-like glycosaminoglycans that are isolated from animal tissues or any polysaccharides that mimic the biological activities of heparin [100]. The main property of heparin, determining its use as an anticoagulant in cardiac surgery, cardiovascular disease, cancer, autoimmune diseases, neurodegenerative diseases, and sepsis-associated coagulopathy [99,101], is its ability to bind and activate antithrombin. Heparin could be an alternative antithrombotic and anti-inflammatory median to prevent PE, especially associated to thrombophilia [78]; however, evidence on the efficacy is conflicting.…”

“…LMWH may have other positive impacts on the placental vascular system [103]. In particular, there is strong evidence that heparin and heparinoids may protect the eGC by interacting with N-and 6-O-sulfated HS domains [99], and act as heparinase inhibitors [104]. Another aspect is that UFH and heparan sulfate both bind to and react to cytokines, seemingly acting as messengers but potentially maintaining homeostasis by pulling the cytokines out of circulation, and reduce inflammatory background [105].…”

“…A potential ability to protect or restore the eGC was noted in several chemical substances: protein C, antithrombin, exogenous eGC substituents (HA and chondroitin sulfate), pentosan polysulfate, wheat germ agglutinin, rhamnan sulfate, micro RNAs, anti-TNFα agents, and synthetic antimicrobial peptides [12,16,87,99,104]. However, all these substances have been assessed only in isolated organs or animal studies; therefore, their targeted use for protection of eGC in humans cannot be recommended yet, and further research is needed [87].…”

Science‐in‐brief: The role of the glycocalyx in critically ill patients with reference to the horse

“…New treatment approaches include glycocalyx components and enzyme inhibitors to prevent shedding, factors to accelerate angiogenesis and nanomaterial and glycocalyx‐mimetic biomaterials. Results of clinical trials are still outstanding 44 …”