What is the glycocalyx?
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Understanding the Glycocalyx: Structure, Function, and Clinical Significance
Structure of the Glycocalyx
The glycocalyx is a highly charged, gel-like layer that covers the luminal surface of vascular endothelial cells and other cell types. It is composed of membrane-bound biological macromolecules, including proteoglycans, glycosaminoglycans, glycoproteins, and adherent plasma proteins1 2 4. This complex structure serves as a barrier between the cell and its surroundings, protecting the cell membrane from physical forces and stresses, and maintaining its integrity2.
Functional Roles of the Glycocalyx
Vascular Homeostasis and Permeability
The glycocalyx plays a crucial role in maintaining vascular homeostasis. It controls vascular permeability, regulates microvascular tone, and prevents microvascular thrombosis1 4. The endothelial glycocalyx, which projects into the vascular lumen, separates the vascular wall from circulating blood, thereby participating in mechanosensation and mechanotransduction of blood flow-dependent shear stress. This process results in the synthesis of nitric oxide and flow-mediated vasodilation4.
Cell Signaling and Interaction
Beyond its structural role, the glycocalyx is involved in cell signaling and interaction. It serves as the local medium within which cell-surface receptors diffuse, assemble, and function, exerting thermodynamic and kinetic control over cell signaling3. The glycocalyx also mediates cell-cell interactions and protects the cell membrane from direct physical forces2.
Immune System Regulation
The glycocalyx is actively involved in immune system regulation. It modulates inflammatory responses, including leukocyte rolling and extravasation, and prevents the extravasation of pathogens such as bacteria and viruses4 8. This protective function is critical in maintaining vascular integrity and preventing infections.
Glycocalyx in Disease and Therapeutics
Sepsis and Glycocalyx Degradation
During sepsis, the glycocalyx is degraded by inflammatory mechanisms involving metalloproteinases, heparanase, and hyaluronidase, which are activated by reactive oxygen species and pro-inflammatory cytokines1. This degradation leads to vascular hyper-permeability, unregulated vasodilation, microvessel thrombosis, and augmented leukocyte adhesion. Clinical studies have shown a correlation between blood levels of glycocalyx components and organ dysfunction, severity, and mortality in sepsis1.
Cancer and Tumor Microenvironment
In cancer, changes in the glycocalyx structure are linked to tumor progression and metastasis. The glycocalyx on tumor cells promotes tumor metastasis, while the endothelial glycocalyx acts as a barrier to tumor cell adhesion and transmigration5. Extracellular vesicles (EVs) secreted by tumor cells can modify the glycocalyx, facilitating the development of the tumor microenvironment and promoting angiogenesis and metastasis5.
Vascular Diseases
The glycocalyx is continuously exposed to shear stress and circulating enzymes, leading to its degradation and renovation. An imbalance favoring degradation is associated with various pathologies, including atherosclerosis, hypertension, vascular aging, metastatic cancer, and diabetic vasculopathies4. Research efforts are focused on understanding the mechanisms that promote glycocalyx degradation and developing therapeutic approaches to improve glycocalyx integrity4.
Conclusion
The glycocalyx is a multifunctional and dynamic structure that plays a vital role in vascular homeostasis, cell signaling, immune regulation, and disease progression. Understanding its structure and functions can provide insights into various physiological and pathological processes, paving the way for novel diagnostic and therapeutic strategies. Ongoing research is essential to fully elucidate the mechanisms underlying glycocalyx function and degradation, and to develop effective treatments for related diseases.
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Most relevant research papers on this topic
The glycocalyx: a novel diagnostic and therapeutic target in sepsis
Glycocalyx degradation in sepsis leads to vascular hyperpermeability, unregulated vasodilation, microvessel thrombosis, and augmented leukocyte adhesion, with blood levels of glycocalyx components correlated with organ dysfunction, severity, and mortality.
Literature Review
Very Rigorous Journal
Highly CitedStructure of Glycocalyx
Molecular Dynamics simulations can provide insights into the molecular structure and functions of the glycocalyx, which serves as a barrier between cells and their surroundings, and is involved in various diseases.
Physical biology of the cancer cell glycocalyx
Cancer-specific changes in the glycocalyx structure alter receptor function and trigger emergent behaviors in cancer cells.
Highly CitedEndothelial Glycocalyx.
The endothelial glycocalyx plays a crucial role in blood vessel function, regulating permeability, inflammatory responses, and preventing extravasation of pathogens and tumor cells.
Glycocalyx Acts as a Central Player in the Development of Tumor Microenvironment by Extracellular Vesicles for Angiogenesis and Metastasis
Glycocalyx plays a central role in the development of the tumor microenvironment, affecting angiogenesis and metastasis by regulating extracellular vesicles.
Rigorous JournalThe Glycocalyx: A Central Regulator of Vascular Function.
The glycocalyx is a dynamic structure that plays a crucial role in vascular processes, including permeability, inflammation, thrombosis, mechanotransduction, and cytokine signaling.
Endothelial glycocalyx: sweet shield of blood vessels.
The endothelial glycocalyx plays a crucial role in vascular wall homeostasis and regulation, with pathologic loss potentially impairing vascular wall protection and agonist-induced modulation potentially regulating microvascular volume and exchange area.
Highly CitedThe Emerging Role of the Mammalian Glycocalyx in Functional Membrane Organization and Immune System Regulation
The glycocalyx plays a vital role in cellular processes and can be targeted in therapeutic contexts, offering potential for new therapeutic approaches.
Highly CitedQuantitative Super-Resolution Microscopy of the Mammalian Glycocalyx.
Advanced imaging methods reveal nanoscale organization of the mammalian glycocalyx, with enhanced height in response to epithelial-to-mesenchymal transition and oncogenic KRAS activation.
Rigorous JournalHighly CitedStructure and response to flow of the glycocalyx layer.
The glycocalyx layer in endothelial cells plays a crucial role in cellular differentiation by increasing the concentration of fibroblast growth factors and acting as a lever to transfer mechanical stimulus into the cytoplasmic side of endothelial cells.
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