Glycocalyx Impairment in Vascular Disease: Focus on Inflammation

Abstract

The glycocalyx is a complex polysaccharide-protein layer lining the lumen of vascular endothelial cells. Changes in the structure and function of the glycocalyx promote an inflammatory response in blood vessels and play an important role in the pathogenesis of many vascular diseases (e.g., diabetes, atherosclerosis, and sepsis). Vascular endothelial dysfunction is a hallmark of inflammation-related diseases. Endothelial dysfunction can lead to tissue swelling, chronic inflammation, and thrombosis. Therefore, elimination of endothelial inflammation could be a potential target for the treatment of vascular diseases. This review summarizes the key role of the glycocalyx in the inflammatory process and the possible mechanism by which it alleviates this process by interrupting the cycle of endothelial dysfunction and inflammation. Especially, we highlight the roles of different components of the glycocalyx in modulating the inflammatory process, including components that regulate leukocyte rolling, L-selectin binding, inflammasome activation and the signaling interactions between the glycocalyx components and the vascular cells. We discuss how the glycocalyx interferes with the development of inflammation and the importance of preventing glycocalyx impairment. Finally, drawing on current understanding of the role of the glycocalyx in inflammation, we consider a potential strategy for the treatment of vascular diseases.

Inflammation and vascular dysfunction: The negative synergistic combination of diabetes and COVID‐19

“…Endothelial glycocalyx is impaired in diabetic condition, and changes in the structure and function of the glycocalyx promote an inflammatory response. 82 , 83 , 84 An undersulphated glycocalyx may not only increase susceptibility to SARS‐CoV‐2 infection, but would also result in a procoagulant and antifibrinolytic state associated with poorer outcomes. 85 , 86 The competitive action of heparin with heparan sulphate, which is used by SARS‐CoV‐2 to adhere to vascular wall and to bind to ACE2, may explain some of the positive effects of heparin therapy in COVID‐19.…”

The Relevance of Anti-PF4 Antibody Isotypes and Endogenous Glycosaminoglycans and their Relationship with Inflammatory Biomarkers in Pulmonary Embolism Patients

“… 20 The shedding of endothelial glycocalyx has been shown in certain disease states such as sepsis, viral infections and cardiovascular disease as pathogenic factors and recognized to have diagnostic or prognostic implications. 21 However, their relevance has not been determined in large scale studies. In this regard, Heparin Red probe is a novel fluorescence assay which quantifies polyanionic sulfated GAGs with a sensitivity range of 0-6 µg/ml.…”

Low-Molecular-Weight Heparin Versus Aspirin in Early Management of Acute Ischemic Stroke: A Systematic Review and Meta-Analysis

“…Glycocalyx, a polysaccharide protein complex that covers the surface of vascular endothelial cells, is abundantly expressed on the endothelial cells of the BBB and has been shown to regulate BBB permeability (51). It plays a key role in the inflammatory process by interrupting the cycle of endothelial dysfunction and inflammation (56). After stroke, endothelial cells are exposed to neuroinflammation and elicit degradation of the glycocalyx (57)(58)(59).…”