Loss of Endothelial Glycocalyx Hyaluronan Impairs Endothelial Stability and Adaptive Vascular Remodeling after Arterial Ischemia

Wang, Gangqi; Vries, Margreet R. de; Sol, Wendy; Oeveren‐Rietdijk, Annemarie M. van; Boer, Hetty C. de; Zonneveld, Anton Jan van; Quax, Paul H.A.; Rabelink, Ton J.

doi:10.3390/cells9040824

Cited by 13 publications

(6 citation statements)

References 36 publications

(48 reference statements)

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“…While the activation of Tie2 protects the diabetic mice from the development of proteinuria, loss of GFR, and glomerular histopathological changes, this may be due to the activation that initiates the signaling events of PI3K and AKT, which increases eNOS phosphorylation and local NO production ( Carota et al, 2019 ). Consistently, the reduced Ang1/Tie2 signaling leads to increased unstable glomerular capillaries in hyaluronan synthase 2 knockout mouse model ( van den Berg et al, 2019 ; Wang et al, 2020 ). The potential mechanism may be the loss of hyaluronan that impaired the interaction between endothelial cells and pericytes.…”

Section: Other Angiogenic Factors Associated With Dnmentioning

confidence: 60%

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

et al. 2020

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Diabetic nephropathy (DN) is an important public health concern of increasing proportions and the leading cause of end-stage renal disease (ESRD) in diabetic patients. It is one of the most common long-term microvascular complications of diabetes mellitus that is characterized by proteinuria and glomerular structural changes. Angiogenesis has long been considered to contribute to the pathogenesis of DN, whereas the molecular mechanisms of which are barely known. Angiogenic factors associated with angiogenesis are the major candidates to explain the microvascular and pathologic finds of DN. Vascular endothelial growth factor A (VEGF-A), leucine-rich α-2-glycoprotein 1, angiopoietins and vasohibin family signal between the podocytes, endothelium, and mesangium have important roles in the maintenance of renal functions. An appropriate amount of VEGF-A is beneficial to maintaining glomerular structure, while excessive VEGF-A can lead to abnormal angiogenesis. LRG1 is a novel pro-angiogenic factors involved in the abnormal angiogenesis and renal fibrosis in DN. The imbalance of Ang1/Ang2 ratio has a role in leading to glomerular disease. Vasohibin-2 is recently shown to be in diabetes-induced glomerular alterations. This review will focus on current understanding of these angiogenic factors in angiogenesis and pathogenesis associated with the development of DN, with the aim of evaluating the potential of anti-angiogenesis therapy in patients with DN.

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Section: Other Angiogenic Factors Associated With Dnmentioning

confidence: 60%

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

et al. 2020

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“…11,12 In particular, diabetes and dysregulated glucose metabolism is characterized by significant alterations of the glycocalyx and its components. [13][14][15][16][17] These roles are determined by composition, structure, and relative abundance. Components of the glycocalyx regulate many important physiological processes including outside-in signaling, immune cell recruitment, angiogenesis, and coagulation, together playing a key role in vascular integrity.…”

Section: Introductionmentioning

confidence: 99%

Hyaluronan and Its Receptors as Regulatory Molecules of the Endothelial Interface

Queisser

Mellema

Petrey

2020

J Histochem Cytochem.

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On the surface of endothelial cells (ECs) lies the glycocalyx, a barrier of polysaccharides that isolates the ECs from the blood. The role of the glycocalyx is dynamic and complex, thanks to not only its structure, but its vast number of components, one being hyaluronan (HA). HA is a critical component of the glycocalyx, having been found to have a wide variety of functions depending on its molecular weight, its modification, and receptor–ligand interactions. As HA and viscous blood are in constant contact, HA can transmit mechanosensory information directly to the cytoskeleton of the ECs. The degradation and synthesis of HA directly alters the permeability of the EC barrier; HA modulation not only alters the physical barrier but also can signal the initiation of other pathways. EC proliferation and angiogenesis are in part regulated by HA fragmentation, HA-dependent receptor binding, and downstream signals. The interaction between the CD44 receptor and HA is a driving force behind leukocyte recruitment, but each class of leukocyte still interacts with HA in unique ways during inflammation. HA regulates a diverse repertoire of EC functions.

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“…Further studies are needed to determine how to maximize the benefits of exosomes and microvesicles without untoward negative effects. Hyaluronan is one of the main structural components of the endothelial glycocalyx (31). Hyaluronan synthases (HAS1, HAS2, HAS3) are present at the inner face of the plasma membrane and secretes hyaluronan into the extracellular space, therefore playing a key role in synthesis of the endothelial glycocalyx (32).…”

Section: Discussionmentioning

confidence: 99%

Exosomes and Microvesicles From Adipose-Derived Mesenchymal Stem Cells Protects the Endothelial Glycocalyx From LPS Injury

Taghavi

Abdullah

Shaheen

et al. 2023

Shock

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Introduction: Endothelial glycocalyx damage occurs in numerous pathological conditions and results in endotheliopathy. Extracellular vesicles, including exosomes and microvesicles, isolated from adipose-derived mesenchymal stem cells (ASCs) have therapeutic potential in multiple disease states; however, their role in preventing glycocalyx shedding has not been defined. We hypothesized that ASC-derived exosomes and microvesicles would protect the endothelial glycocalyx from damage by LPS injury in cultured endothelial cells. Methods: Exosomes and microvesicles were collected from ASC conditioned media by centrifugation (10,000g for microvesicles, 100,000g for exosomes). Human umbilical vein endothelial cells (HUVECs) were exposed to 1 μg/mL lipopolysaccharide (LPS). LPS-injured cells (n = 578) were compared with HUVECS with concomitant LPS injury plus 1.0 μg/mL of exosomes (n = 540) or microvesicles (n = 510) for 24 hours. These two cohorts were compared with control HUVECs that received phosphate-buffered saline only (n = 786) and HUVECs exposed to exosomes (n = 505) or microvesicles (n = 500) alone. Cells were fixed and stained with FITC-labeled wheat germ agglutinin to quantify EGX. Real-time quantitative reverse-transcription polymerase chain reaction was used on HUVECs cell lystate to quantify hyaluron synthase-1 (HAS1) expression. Results: Exosomes alone decreased endothelial glycocalyx staining intensity when compared with control (4.94 vs. 6.41 AU, P < 0.001), while microvesicles did not cause a change glycocalyx staining intensity (6.39 vs. 6.41, P = 0.99). LPS injury resulted in decreased glycocalyx intensity as compared with control (5.60 vs. 6.41, P < 0.001). Exosomes (6.85 vs. 5.60, P < 0.001) and microvesicles (6.35 vs. 5.60, P < 0.001) preserved endothelial glycocalyx staining intensity after LPS injury. HAS1 levels were found to be higher in the exosome (1.14 vs. 3.67 RE, P = 0.02) and microvesicle groups (1.14 vs. 3.59 RE, P = 0.02) when compared with LPS injury. Hyaluron synthase-2 and synthase-3 expressions were not different in the various experimental groups. Conclusions: Exosomes alone can damage the endothelial glycocalyx. However, in the presence of LPS injury, both exosomes and microvesicles protect the glycocalyx layer. This effect seems to be mediated by HAS1.

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Loss of Endothelial Glycocalyx Hyaluronan Impairs Endothelial Stability and Adaptive Vascular Remodeling after Arterial Ischemia

Cited by 13 publications

References 36 publications

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

Role of VEGF-A and LRG1 in Abnormal Angiogenesis Associated With Diabetic Nephropathy

Hyaluronan and Its Receptors as Regulatory Molecules of the Endothelial Interface

Exosomes and Microvesicles From Adipose-Derived Mesenchymal Stem Cells Protects the Endothelial Glycocalyx From LPS Injury

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