Endothelial Glycocalyx

PIGO‐CDG: A case study with a new genotype, expansion of the phenotype, literature review, and nosological considerations

“…The severe feeding intolerance with lack of weight gain despite numerous enteral regimens is also striking and, in conjunction with a possible decreased intestinal water reabsorption, may point to a generalized small bowel mucosal dysfunction caused by the deficiency of GPI‐anchored proteins in this patient. We hypothesize that a possible mechanism for this intestinal failure may include loss of glycocalyx‐associated proteins at the enteral mucosa, such as loss of glypicans and glypican‐bound heparan sulfate at the mucosal capillaries leading to increased extravasation of fluid from the intravascular to the intestinal luminal compartment 18,19 . Glycocalyceal dysfunction has been previously suggested as a pathogenic mechanism in a cohort of patients with congenital disorders of glycosylation, including a patient with PIGN‐CDG reported by Brucker et al for whom fresh frozen plasma and protein C concentrate infusions were given, with the rationale of supporting the endothelial glycocalyx during acute illnesses, with excellent results 20 .…”

“…We hypothesize that a possible mechanism for this intestinal failure may include loss of glycocalyx-associated proteins at the enteral mucosa, such as loss of glypicans and glypican-bound heparan sulfate at the mucosal capillaries leading to increased extravasation of fluid from the intravascular to the intestinal luminal compartment. 18,19 Glycocalyceal dysfunction has been previously suggested as a pathogenic mechanism in a cohort of patients with congenital disorders of glycosylation, including a patient with PIGN-CDG reported by Brucker et al for whom fresh frozen plasma and protein C concentrate infusions were given, with the rationale of supporting the endothelial glycocalyx during acute illnesses, with excellent results. 20 It is possible that further studies, especially using the recently validated murine model for PIGO deficiency, 21 will better delineate the role of the glycocalyx and the etiology of intestinal dysfunction in these patients and provide therapeutic insights for addressing this issue.…”

Disruption of the endothelial glycocalyx layer is associated with idiopathic complete atrioventricular block in the elderly population: An observational pilot study

“…22 The glycocalyx layer consists of glycoproteins and proteoglycans that regulate properties such as intercellular communication, electrostatic charge, ionic buffering, vascular permeability, and mechanosense–mechanotransduction. 11 The physical relationship of the components of EG to the vessel lumen allows them to participate in mechanosensation–mechanotransduction of blood flow-induced shear stress, resulting in nitric oxide synthesis and flow-mediated vasodilation. 11 The EG also participates in the regulation of vascular permeability and the regulation of inflammatory processes, including leukocyte rolling and extravasation processes.…”

“…11 The physical relationship of the components of EG to the vessel lumen allows them to participate in mechanosensation–mechanotransduction of blood flow-induced shear stress, resulting in nitric oxide synthesis and flow-mediated vasodilation. 11 The EG also participates in the regulation of vascular permeability and the regulation of inflammatory processes, including leukocyte rolling and extravasation processes. 12 In addition, endothelial glycocalic degradation is a marker of vascular aging, and because of these features, glycocalic degradation plays an important role in the induction of profibrotic processes in the body.…”

“…The balance to the direction of deterioration is increased in a variety of pathological conditions, including atherosclerosis, hypertension, vascular aging, metastatic cancer, and diabetic vasculopathies. 11 Shedding of EG plays a central role in many critical illnesses, and disruption of EG is associated with increased morbidity and mortality. During acute injury, inflammatory events, or many other pathological conditions, the EG is damaged and building blocks of the glycocalyx layer, such as syndecan-1 (SDC1/sCD138) leak into the circulation.…”