Glycocalyx–Sodium Interaction in Vascular Endothelium

Abstract

The glycocalyx generally covers almost all cellular surfaces, where it participates in mediating cell-surface interactions with the extracellular matrix as well as with intracellular signaling molecules. The endothelial glycocalyx that covers the luminal surface mediates the interactions of endothelial cells with materials flowing in the circulating blood, including blood cells. Cardiovascular diseases (CVD) remain a major cause of morbidity and mortality around the world. The cardiovascular risk factors start by causing endothelial cell dysfunction associated with destruction or irregular maintenance of the glycocalyx, which may culminate into a full-blown cardiovascular disease. The endothelial glycocalyx plays a crucial role in shielding the cell from excessive exposure and absorption of excessive salt, which can potentially cause damage to the endothelial cells and underlying tissues of the blood vessels. So, in this mini review/commentary, we delineate and provide a concise summary of the various components of the glycocalyx, their interaction with salt, and subsequent involvement in the cardiovascular disease process. We also highlight the major components of the glycocalyx that could be used as disease biomarkers or as drug targets in the management of cardiovascular diseases.

ADAMTS5 Promotes Permeability of the Blood-Brain Barrier during Treponema pallidum Subspecies pallidum Invading the Central Nervous System

“…Subsequently, we investigated the role of ADAMTS5 in Tp-induced endothelial glycocalyx damage in vitro. Immunofluorescence analysis showed a significant reduction in wheat germ agglutinin (WGA), which bounded to N -acetylglucosamine sugar residues (a component of hyaluronic acid) , and syndecan-1 on the surface of hCMEC/D3 cells following Tp stimulation (Figure A). Importantly, this reduction was mitigated after pretreatment with the ADAMTS5 inhibitor (Figure A).…”

“…Since our study found that IL-1β regulated ADAMTS5 in hCMEC/D3 cells and inhibiting IL-1β was beneficial to reducing ADAMTS5 expression, the application of IL-1β inhibitors or knockdown of IL-1β could be considered in subsequent studies to protect the glycocalyx of hCMEC/D3 cells. In addition, the regulatory mechanism of the endothelial glycocalyx, such as syndecan-1 and hyaluronic acid, was complicated and affected by multiple factors. Previous studies confirmed that the cysteine-rich domain of ADAMTS5 was important in contacting glycosaminoglycans in aggrecan, and the ADAMTS5 spacer domain interacted with the aggrecan protein core. , However, whether there were similar domain recognition processes during the decomposition of the endothelial glycocalyx, such as syndecan-1 and hyaluronic acid, by ADAMTS5 remained unclear and needed further exploration.…”

“…However, previous research indicated that ADAMTS5 could compromise the endothelial glycocalyx, leading to vascular endothelial dysfunction. 23 To study the role of ADAMTS5 in the dysfunction of the barrier, we determined the expression of syndecan-1, which represented a major breakdown product of the glycocalyx, 24 and hyaluronic acid in the CSF from HIV-negative patients with neurosyphilis. Results showed that both syndecan-1 and hyaluronic acid protein levels were notably up-regulated compared to the control (Figure 5A,B).…”

“…24 This layer formed a gel-like substance on the surface of endothelial cells. 24 The endothelial glycocalyx could maintain the vascular system by regulating vascular permeability and microvascular tension, preventing thrombosis, and controlling leukocyte adhesion. 25,26 However, when the normal structure of the endothelial glycocalyx was compromised, these functions were impaired, potentially contributing to the development of various diseases.…”

“…The endothelial glycocalyx was an extracellular matrix layer that covered the surface of endothelial cells, primarily composed of heparan sulfate, chondroitin sulfate, and hyaluronic acid . This layer formed a gel-like substance on the surface of endothelial cells . The endothelial glycocalyx could maintain the vascular system by regulating vascular permeability and microvascular tension, preventing thrombosis, and controlling leukocyte adhesion. , However, when the normal structure of the endothelial glycocalyx was compromised, these functions were impaired, potentially contributing to the development of various diseases. , …”