TNF-α induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin

Chappell, Daniel; Hofmann-Kiefer, Klaus; Jacob, Matthias; Rehm, Markus; Briegel, Josef; Welsch, Ulrich; Conzen, Peter; Becker, Bernhard F.

doi:10.1007/s00395-008-0749-5

Cited by 252 publications

(261 citation statements)

References 49 publications

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“…Therefore, glycocalyx destruction can have direct effects on coagulation and fibrinolytic responses as well as leukocyte adhesion, and it induces an impairment of shear stress-dependent nitric oxide production in arteries and cultured endothelial cells. [44][45][46][47][48][49][50][51][52] Disruption of this structure can lead to capillary flow impairment and by extrapolation, similar phenomena downstream.…”

Section: Discussionmentioning

confidence: 99%

“…62 Also, TNF-a is able to induce rapid shedding of the endothelial glycocalyx in the intact coronary vascular system. 50 Taking all these elements together, IS-induced loss of glycocalyx could be a logical explanation for the observed disrupted blood flow. The negative charge of blood cells prevents them from adhering to the vessel wall, which itself carries a negative charge imparted by the endothelial glycocalyx.…”

Section: Discussionmentioning

confidence: 99%

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Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Pletinck

Glorieux

Schepers

et al. 2013

Journal of the American Society of Nephrology

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Leukocyte activation and endothelial damage both contribute to cardiovascular disease, a major cause of morbidity and mortality in CKD. Experimental in vitro data link several protein-bound uremic retention solutes to the modulation of inflammatory stimuli, including endothelium and leukocyte responses and cardiovascular damage, corroborating observational in vivo data. However, the impact of these uremic toxins on the crosstalk between endothelium and leukocytes has not been assessed. This study evaluated the effects of acute and continuous exposure to uremic levels of indoxylsulfate (IS), p-cresylsulfate (pCS), and p-cresylglucuronide (pCG) on the recruitment of circulating leukocytes in the rat peritoneal vascular bed using intravital microscopy. Superfusion with IS induced strong leukocyte adhesion, enhanced extravasation, and interrupted blood flow, whereas pCS caused a rapid increase in leukocyte rolling. Superfusion with pCS and pCG combined caused impaired blood flow and vascular leakage but did not further enhance leukocyte rolling over pCS alone. Intravenous infusion with IS confirmed the superfusion results and caused shedding of heparan sulfate, pointing to disruption of the glycocalyx as the mechanism likely mediating IS-induced flow stagnation. These results provide the first clear in vivo evidence that IS, pCS, and pCG exert proinflammatory effects that contribute to vascular damage by stimulating crosstalk between leukocytes and vessels.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Pletinck

Glorieux

Schepers

et al. 2013

Journal of the American Society of Nephrology

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“…In an isolated heart model, hydrocortisone significantly reduced the shedding of the endothelial surface layer after ischaemia, reperfusion and TNF-a infusion [22,36]. Prophylactic intra-operative glucocorticoids did not benefit patients undergoing cardiac surgery [49].…”

Section: Damage To the Endothelial Surface Layermentioning

confidence: 97%

The endothelial glycocalyx: a review of the vascular barrier

Alphonsus¹,

2014

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SummaryThe endothelial glycocalyx is an important part of the vascular barrier. The glycocalyx is intimately linked to the homoeostatic functions of the endothelium. Damage to the glycocalyx precedes vascular pathology. In the first part of this paper, we have reviewed the structure, physiology and pathology of the endothelial glycocalyx, based on a literature search of the past five years. In the second part, we have systematically reviewed interventions to protect or repair the glycocalyx. Glycocalyx damage can be caused by hypervolaemia and hyperglycaemia and can be prevented by maintaining a physiological concentration of plasma protein, particularly albumin.

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“…Glycocalyx shedding under severe inflammatory conditions, such as postischemic reperfusion, can be prevented using various treatments, e.g., hydrocortisone, antithrombin, or heparin (35,36). Sulodexide, a mix of heparan sulfate and dermatan sulfate, increases glycocalyx thickness in type 2 diabetes (14).…”

Section: Lack Of Hyal1 Maintains Glycocalyx Structure and Prevents Hamentioning

confidence: 99%

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

et al. 2016

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Hyaluronic acid (HA) is a major component of the glycocalyx involved in the vascular wall and endothelial glomerular permeability barrier. Endocytosed hyaluronidase HYAL1 is known to degrade HA into small fragments in different cell types, including endothelial cells. In diabetes, the size and permeability of the glycocalyx are altered. In addition, patients with type 1 diabetes present increased plasma levels of both HA and HYAL1. To investigate the potential implication of HYAL1 in the development of diabetes-induced endothelium dysfunction, we measured endothelial markers, endothelium-dependent vasodilation, arteriolar glycocalyx size, and glomerular barrier properties in wild-type and HYAL1 knockout (KO) mice with or without streptozotocin (STZ)-induced diabetes. We observed that 4 weeks after STZ injections, the lack of HYAL1 1) prevents diabetes-induced increases in soluble P-selectin concentrations and limits the impact of the disease on endothelium-dependent hyperpolarization (EDH)-mediated vasorelaxation; 2) increases glycocalyx thickness and maintains glycocalyx structure and HA content during diabetes; and 3) prevents diabetes-induced glomerular barrier dysfunction assessed using the urinary albumin-to-creatinine ratio and urinary ratio of 70-to 40-kDa dextran. Our findings suggest that HYAL1 contributes to endothelial and glycocalyx dysfunction induced by diabetes. HYAL1 inhibitors could be explored as a new therapeutic approach to prevent vascular complications in diabetes.

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TNF-α induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin

Cited by 252 publications

References 49 publications

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

Protein-Bound Uremic Toxins Stimulate Crosstalk between Leukocytes and Vessel Wall

The endothelial glycocalyx: a review of the vascular barrier

Hyaluronidase 1 Deficiency Preserves Endothelial Function and Glycocalyx Integrity in Early Streptozotocin-Induced Diabetes

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