Glycocalyx glycosaminoglycans (GAGs)

The endothelial glycocalyx is a complex, carbohydrate-rich layer coating the luminal surface of vascular endothelial cells, primarily composed of glycosaminoglycans (GAGs) such as heparan sulfate, chondroitin sulfate, and hyaluronan (Uchimido et al., 2019, Journal of Intensive Care). These molecules are essential for maintaining vascular homeostasis, serving as a semi-permeable barrier that regulates fluid and macromolecule flux, and acting as a scaffold for signaling molecules and anticoagulants like antithrombin (Reihani et al., 2019, Frontiers in Medicine). Heparin, a highly sulfated GAG, is widely used clinically as an anticoagulant because it binds to antithrombin III, dramatically increasing its ability to neutralize thrombin and Factor Xa (StatPearls, 2023). In pathological states like sepsis, trauma, and diabetes, the glycocalyx is often degraded or "shed," leading to increased vascular permeability, edema, and unregulated inflammation (NIH, 2021). Therapeutic interventions focus on either utilizing GAGs for anticoagulation, neutralizing them in cases of overdose (e.g., with protamine), or developing "glycocalyx-protective" therapies to maintain endothelial integrity during critical illness.

Other names

HeparinHeparan sulfateChondroitin sulfateDermatan sulfateHyaluronanEndothelial glycocalyxHeparin and related glycocalyx glycosaminoglycans

Drugs targeting these molecules primarily act by binding to and potentiating antithrombin III to inhibit clotting factors like thrombin and Factor Xa, or by acting as mimetics to restore the endothelial barrier and neutralize pro-inflammatory mediators.