Roles of Endovascular Calyx Related Enzymes in Endothelial Dysfunction and Diabetic Vascular Complications

Li, Zhi; Wu, Ning; Wang, Jing; Zhang, Quanbin

doi:10.3389/fphar.2020.590614

Cited by 13 publications

(8 citation statements)

References 131 publications

(210 reference statements)

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“…The three main factors reported to result in glycocalyx degradation in diabetes are reactive oxygen species (ROS), advanced glycation end products and sheddase activation. Both ROS and advanced glycation end products depolymerize hyaluronan, causing a damage in the glycocalyx integrity, while sheddases, like hyaluronidase, heparinase, metalloproteinase and neuraminidase, cleave glycocalyx components (Figure 3) (117). Notably, all these factors are increased in plasma of diabetic patients, which indicates a strong correlation between glycocalyx damage and insulin resistance (118)(119)(120).…”

Section: Endothelial Glycocalyx Damage and Its Link To Risk Factors O...mentioning

confidence: 98%

The Endothelial Glycocalyx: A Possible Therapeutic Target in Cardiovascular Disorders

Milusev

Rieben

Sorvillo

2022

Front. Cardiovasc. Med.

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The physiological, anti-inflammatory, and anti-coagulant properties of endothelial cells (ECs) rely on a complex carbohydrate-rich layer covering the luminal surface of ECs, called the glycocalyx. In a range of cardiovascular disorders, glycocalyx shedding causes endothelial dysfunction and inflammation, underscoring the importance of glycocalyx preservation to avoid disease initiation and progression. In this review we discuss the physiological functions of the glycocalyx with particular focus on how loss of endothelial glycocalyx integrity is linked to cardiovascular risk factors, like hypertension, aging, diabetes and obesity, and contributes to the development of thrombo-inflammatory conditions. Finally, we consider the role of glycocalyx components in regulating inflammatory responses and discuss possible therapeutic interventions aiming at preserving or restoring the endothelial glycocalyx and therefore protecting against cardiovascular disease.

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Section: Endothelial Glycocalyx Damage and Its Link To Risk Factors O...mentioning

confidence: 98%

The Endothelial Glycocalyx: A Possible Therapeutic Target in Cardiovascular Disorders

Milusev

Rieben

Sorvillo

2022

Front. Cardiovasc. Med.

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“…Several studies reported the ability of matrix metalloproteinases (MMP) to cleave syndecans, an essential component of proteoglycans. For example, MMP-9, which commonly causes SDC-1 degradation, or MMP-2, that induces the cleavage of SDC-4 [54]. It seems that the action of MMPs is facilitated by the loss of HS.…”

Section: Endothelial Glycocalyx and Sepsismentioning

confidence: 99%

“…Furthermore, low molecular hyaluronic acid fragments produce the expression of vascular cell-adhesion molecule -1 (VCAM-1) and intercellular-adhesion molecule -1 (ICAM-1), resulting in increased macrophage activity, as well as inflammation and endothelial cell damage [57]. These processes may be modulated by the activation of extracellular heparanases by proinflammatory cytokines [54]. Particularly in humans, the endo-β-glucuronidase Heparanase-1 (Hpa-1) is decreased during sepsis and has been proposed as a biomarker to predict the risk of sepsis in adults [58].…”

Section: Endothelial Glycocalyx and Sepsismentioning

confidence: 99%

The Endothelial Glycocalyx and Neonatal Sepsis

Fatmi

Saadi

Beltrán-García

et al. 2022

IJMS

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Sepsis carries a substantial risk of morbidity and mortality in newborns, especially preterm-born neonates. Endothelial glycocalyx (eGC) is a carbohydrate-rich layer lining the vascular endothelium, with important vascular barrier function and cell adhesion properties, serving also as a mechano-sensor for blood flow. eGC shedding is recognized as a fundamental pathophysiological process generating microvascular dysfunction, which in turn contributes to multiple organ failure and death in sepsis. Although the disruption of eGC and its consequences have been investigated intensively in the adult population, its composition, development, and potential mechanisms of action are still poorly studied during the neonatal period, and more specifically, in neonatal sepsis. Further knowledge on this topic may provide a better understanding of the molecular mechanisms that guide the sepsis pathology during the neonatal period, and would increase the usefulness of endothelial glycocalyx dysfunction as a diagnostic and prognostic biomarker. We reviewed several components of the eGC that help to deeply understand the mechanisms involved in the eGC disruption during the neonatal period. In addition, we evaluated the potential of eGC components as biomarkers and future targets to develop therapeutic strategies for neonatal sepsis.

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“…ADAMs can cleave syndecans, one of the major constituents of eGCX, cytokine receptors, and cell adhesion molecules expressed by endothelial cells and leukocytes ( 14 ). As to heparanase, it is capable of degrading heparin sulfate moieties, further aggravating the disruption of eGCX ( 13 , 15 ). According to the study by Schmidt, et al., eGCX degradation involves the specific loss of heparin sulfate caused by endothelial stored heparanase, a TNF-α–responsive, heparin sulfate–specific glucuronidase ( 12 ).…”

Section: The Role Of Egcx In Lung Diseasesmentioning

confidence: 99%

Endothelial glycocalyx in hepatopulmonary syndrome: An indispensable player mediating vascular changes

Cook

Liu

et al. 2022

Front. Immunol.

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Hepatopulmonary syndrome (HPS) is a serious pulmonary vascular complication that causes respiratory insufficiency in patients with chronic liver diseases. HPS is characterized by two central pathogenic features—intrapulmonary vascular dilatation (IPVD) and angiogenesis. Endothelial glycocalyx (eGCX) is a gel-like layer covering the luminal surface of blood vessels which is involved in a variety of physiological and pathophysiological processes including controlling vascular tone and angiogenesis. In terms of lung disorders, it has been well established that eGCX contributes to dysregulated vascular contraction and impaired blood-gas barrier and fluid clearance, and thus might underlie the pathogenesis of HPS. Additionally, pharmacological interventions targeting eGCX are dramatically on the rise. In this review, we aim to elucidate the potential role of eGCX in IPVD and angiogenesis and describe the possible degradation-reconstitution equilibrium of eGCX during HPS through a highlight of recent literature. These studies strongly underscore the therapeutic rationale in targeting eGCX for the treatment of HPS.

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Roles of Endovascular Calyx Related Enzymes in Endothelial Dysfunction and Diabetic Vascular Complications

Cited by 13 publications

References 131 publications

The Endothelial Glycocalyx: A Possible Therapeutic Target in Cardiovascular Disorders

The Endothelial Glycocalyx: A Possible Therapeutic Target in Cardiovascular Disorders

The Endothelial Glycocalyx and Neonatal Sepsis

Endothelial glycocalyx in hepatopulmonary syndrome: An indispensable player mediating vascular changes

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