scholarly journals Endothelial pathophysiology, glycosaminoglycans and glycocalyx

2015 ◽  
Vol 4 (4S) ◽  
pp. 5-16
Author(s):  
Luca Masotti
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Structural Properties ◽  
Vascular Diseases ◽  
Endothelial Glycocalyx ◽  
Luminal Surface ◽  
The Past ◽  
Physiological Processes ◽  
Inflammatory Processes ◽  
Membrane Bound

The endothelial glycocalyx can be described as a network of membrane-bound proteoglycans and glycoproteins, covering the luminal surface of endothelial cells. Over the past decades, structural properties and functions of glycocalyx have been increasingly examined, underlining its role in many physiological processes. This article provides the basis on composition and functions of the endothelial glycocalyx. The Author also describes the so called “endothelial dysfunction” and how it can lead to the development of pathological inflammatory processes and consequent vascular diseases.

scholarly journals Endothelial Dysfunction in Fabry Disease Is Related to Glycocalyx Degradation

2021 ◽  
Vol 12 ◽  
Author(s):  
Solvey Pollmann ◽  
David Scharnetzki ◽  
Dominique Manikowski ◽  
Malte Lenders ◽  
Eva Brand
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Fabry Disease ◽  
Specific Inhibitor ◽  
Small Vessel ◽  
Endothelial Glycocalyx ◽  
Enzyme Replacement ◽  
Anti Inflammatory

Fabry disease (FD) is an X-linked multisystemic lysosomal storage disease due to a deficiency of α-galactosidase A (GLA/AGAL). Progressive cellular accumulation of the AGAL substrate globotriaosylceramide (Gb3) leads to endothelial dysfunction. Here, we analyzed endothelial function in vivo and in vitro in an AGAL-deficient genetic background to identify the processes underlying this small vessel disease. Arterial stiffness and endothelial function was prospectively measured in five males carrying GLA variants (control) and 22 FD patients under therapy. AGAL-deficient endothelial cells (EA.hy926) and monocytes (THP1) were used to analyze endothelial glycocalyx structure, function, and underlying inflammatory signals. Glycocalyx thickness and small vessel function improved significantly over time (p<0.05) in patients treated with enzyme replacement therapy (ERT, n=16) and chaperones (n=6). AGAL-deficient endothelial cells showed reduced glycocalyx and increased monocyte adhesion (p<0.05). In addition, increased expression of angiopoietin-2, heparanase and NF-κB was detected (all p<0.05). Incubation of wild-type endothelial cells with pathological globotriaosylsphingosine concentrations resulted in comparable findings. Treatment of AGAL-deficient cells with recombinant AGAL (p<0.01), heparin (p<0.01), anti-inflammatory (p<0.001) and antioxidant drugs (p<0.05), and a specific inhibitor (razuprotafib) of angiopoietin-1 receptor (Tie2) (p<0.05) improved glycocalyx structure and endothelial function in vitro. We conclude that chronic inflammation, including the release of heparanases, appears to be responsible for the degradation of the endothelial glycocalyx and may explain the endothelial dysfunction in FD. This process is partially reversible by FD-specific and anti-inflammatory treatment, such as targeted protective Tie2 treatment.

scholarly journals Anti-Inflammatory Properties of Sirtuin 6 in Human Umbilical Vein Endothelial Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Martha Lappas
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Histone Deacetylase ◽  
Proinflammatory Cytokines ◽  
Inflammatory Diseases ◽  
Umbilical Vein ◽  
Vascular Diseases ◽  
Transcriptional Level ◽  
Human Umbilical Vein ◽  
Umbilical Vein Endothelial Cells

A prominent feature of inflammatory diseases is endothelial dysfunction. Factors associated with endothelial dysfunction include proinflammatory cytokines, adhesion molecules, and matrix degrading enzymes. At the transcriptional level, they are regulated by the histone deacetylase sirtuin (SIRT) 1 via its actions on the proinflammatory transcription factor nuclear factor-κB (NF-κB). The role of SIRT6, also a histone deacetylase, in regulating inflammation in endothelial cells is not known. The aim of this study was to determine the effect of SIRT6 knockdown on inflammatory markers in human umbilical vein endothelial cells (HUVECs) in the presence of lipopolysaccharide (LPS). LPS decreased expression of SIRT6 in HUVECs. Knockdown of SIRT6 increased the expression of proinflammatory cytokines (IL-1β, IL-6, IL-8), COX-prostaglandin system, ECM remodelling enzymes (MMP-2, MMP-9 and PAI-1), the adhesion molecule ICAM-1, and proangiogenic growth factors VEGF and FGF-2; cell migration; cell adhesion to leukocytes. Loss of SIRT6 increased the expression of NF-κB, whereas overexpression of SIRT6 was associated with decreased NF-κB transcriptional activity. Taken together, these results demonstrate that the loss of SIRT6 in endothelial cells is associated with upregulation of genes involved in inflammation, vascular remodelling, and angiogenesis. SIRT6 may be a potential pharmacological target for inflammatory vascular diseases.

scholarly journals Endothelial Dysfunction and SARS-CoV-2 Infection: Association and Therapeutic Strategies

Pathogens ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 582
Author(s):  
Hai Deng ◽  
Ting-Xuan Tang ◽  
Deng Chen ◽  
Liang-Sheng Tang ◽  
Xiang-Ping Yang ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Platelet Adhesion ◽  
Vascular Dysfunction ◽  
Critical Role ◽  
Therapeutic Strategies ◽  
Leukocyte Activation ◽  
Physiological Processes ◽  
Blood Fluidity ◽  
Systemic Disorder

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), has been recently considered a systemic disorder leading to the procoagulant state. Preliminary studies have shown that SARS-CoV-2 can infect endothelial cells, and extensive evidence of inflammation and endothelial dysfunction has been found in advanced COVID-19. Endothelial cells play a critical role in many physiological processes, such as controlling blood fluidity, leukocyte activation, adhesion, platelet adhesion and aggregation, and transmigration. Therefore, it is reasonable to think that endothelial dysfunction leads to vascular dysfunction, immune thrombosis, and inflammation associated with COVID-19. This article summarizes the association of endothelial dysfunction and SARS-CoV-2 infection and its therapeutic strategies.

scholarly journals Vascular Endothelial Cells: Heterogeneity and Targeting Approaches

Cells ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2712
Author(s):  
Jan K. Hennigs ◽  
Christiane Matuszcak ◽  
Martin Trepel ◽  
Jakob Körbelin
Keyword(s):  
Endothelial Cells ◽  
Immune Cell ◽  
Vascular System ◽  
Vascular Endothelial Cells ◽  
Treatment Options ◽  
Vascular Diseases ◽  
The Body ◽  
Liver Sinusoids ◽  
Physiological Processes ◽  
Organ Systems

Forming the inner layer of the vascular system, endothelial cells (ECs) facilitate a multitude of crucial physiological processes throughout the body. Vascular ECs enable the vessel wall passage of nutrients and diffusion of oxygen from the blood into adjacent cellular structures. ECs regulate vascular tone and blood coagulation as well as adhesion and transmigration of circulating cells. The multitude of EC functions is reflected by tremendous cellular diversity. Vascular ECs can form extremely tight barriers, thereby restricting the passage of xenobiotics or immune cell invasion, whereas, in other organ systems, the endothelial layer is fenestrated (e.g., glomeruli in the kidney), or discontinuous (e.g., liver sinusoids) and less dense to allow for rapid molecular exchange. ECs not only differ between organs or vascular systems, they also change along the vascular tree and specialized subpopulations of ECs can be found within the capillaries of a single organ. Molecular tools that enable selective vascular targeting are helpful to experimentally dissect the role of distinct EC populations, to improve molecular imaging and pave the way for novel treatment options for vascular diseases. This review provides an overview of endothelial diversity and highlights the most successful methods for selective targeting of distinct EC subpopulations.

scholarly journals Modulation of Endothelial Glycocalyx Structure under Inflammatory Conditions

2014 ◽  
Vol 2014 ◽  
pp. 1-17 ◽  
Author(s):  
Hana Kolářová ◽  
Barbora Ambrůzová ◽  
Lenka Švihálková Šindlerová ◽  
Anna Klinke ◽  
Lukáš Kubala
Keyword(s):  
Vessel Wall ◽  
Current Knowledge ◽  
Ischemia Reperfusion ◽  
Theoretical Models ◽  
Endothelial Glycocalyx ◽  
Inflammatory Conditions ◽  
Physiological Processes ◽  
Inflammatory Processes ◽  
Experimental Approaches ◽  
Structure And Functions

The glycocalyx of the endothelium is an intravascular compartment that creates a barrier between circulating blood and the vessel wall. The glycocalyx is suggested to play an important role in numerous physiological processes including the regulation of vascular permeability, the prevention of the margination of blood cells to the vessel wall, and the transmission of shear stress. Various theoretical models and experimental approaches provide data about changes to the structure and functions of the glycocalyx under various types of inflammatory conditions. These alterations are suggested to promote inflammatory processes in vessels and contribute to the pathogenesis of number of diseases. In this review we summarize current knowledge about the modulation of the glycocalyx under inflammatory conditions and the consequences for the course of inflammation in vessels. The structure and functions of endothelial glycocalyx are briefly discussed in the context of methodological approaches regarding the determination of endothelial glycocalyx and the uncertainty and challenges involved in glycocalyx structure determination. In addition, the modulation of glycocalyx structure under inflammatory conditions and the possible consequences for pathogenesis of selected diseases and medical conditions (in particular, diabetes, atherosclerosis, ischemia/reperfusion, and sepsis) are summarized. Finally, therapeutic strategies to ameliorate glycocalyx dysfunction suggested by various authors are discussed.

scholarly journals Endothelial Toxicity of High Glucose and its by-Products in Diabetic Kidney Disease

Toxins ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 578 ◽  
Author(s):  
Dou ◽  
Jourde-Chiche
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Kidney Disease ◽  
High Glucose ◽  
Diabetic Kidney Disease ◽  
Polyol Pathway ◽  
Endothelial Glycocalyx ◽  
Diabetic Kidney ◽  
Filtration Barrier ◽  
By Products

Alterations of renal endothelial cells play a crucial role in the initiation and progression of diabetic kidney disease. High glucose per se, as well as glucose by-products, induce endothelial dysfunction in both large vessels and the microvasculature. Toxic glucose by-products include advanced glycation end products (AGEs), a group of modified proteins and/or lipids that become glycated after exposure to sugars, and glucose metabolites produced via the polyol pathway. These glucose-related endothelio-toxins notably induce an alteration of the glomerular filtration barrier by increasing the permeability of glomerular endothelial cells, altering endothelial glycocalyx, and finally, inducing endothelial cell apoptosis. The glomerular endothelial dysfunction results in albuminuria. In addition, high glucose and by-products impair the endothelial repair capacities by reducing the number and function of endothelial progenitor cells. In this review, we summarize the mechanisms of renal endothelial toxicity of high glucose/glucose by-products, which encompass changes in synthesis of growth factors like TGF-β and VEGF, induction of oxidative stress and inflammation, and reduction of NO bioavailability. We finally present potential therapies to reduce endothelial dysfunction in diabetic kidney disease.

scholarly journals Tetramethylpyrazine Protects against Hydrogen Peroxide-Provoked Endothelial Dysfunction in Isolated Rat Aortic Rings: Implications for Antioxidant Therapy of Vascular Diseases

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Xiaojia Ni ◽  
Siu Ling Wong ◽  
Chi Ming Wong ◽  
Chi Wai Lau ◽  
Xiaogeng Shi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Nadph Oxidase ◽  
Vascular Diseases ◽  
Isometric Tension ◽  
Protective Mechanism ◽  
Enos Expression ◽  
Isolated Rat

Background and Objectives. Oxidative stress can initiate endothelial dysfunction and atherosclerosis. This study evaluated whether tetramethylpyrazine (TMP), the predominant active ingredient in Rhizoma Ligustici Wallichii (chuanxiong), prevents endothelial dysfunction in a rat model of oxidative stress.Methods. Isolated rat aortic rings were pretreated with various drugs before the induction of endothelial dysfunction by hydrogen peroxide (H2O2). Changes in isometric tension were then measured in acetylcholine- (ACh-) relaxed rings. Endothelial nitric oxide synthase (eNOS) expression was evaluated in the rings by Western blotting, and superoxide anion (O2∙-) content was assessed in primary rat aortic endothelial cells by dihydroethidium- (DHE-) mediated fluorescence microscopy.Results. ACh-induced endothelium-dependent relaxation (EDR) was disrupted by H2O2in endothelium-intact aortic rings. H2O2-impaired relaxation was ameliorated by acute pretreatment with low concentrations of TMP, as well as by pretreatment with catalase and the NADPH oxidase inhibitors, apocynin and diphenyleneiodonium (DPI). TMP, apocynin, and DPI also reducedO2∙-accumulation in endothelial cells,but TMP failed to alter eNOS expression in aortic rings incubated with H2O2.Conclusions. TMP safeguards against oxidative stress-induced endothelial dysfunction, suggesting that the agent might find therapeutic utility in the management of vascular diseases. However, TMP’s role in inhibiting NADPH oxidase and its vascular-protective mechanism of action requires further investigation.

scholarly journals Can Endothelial Glycocalyx Be A Major Morphological Substrate in Pre-Eclampsia?

2020 ◽  
Vol 21 (9) ◽  
pp. 3048 ◽  
Author(s):  
Marina M. Ziganshina ◽  
Ekaterina L. Yarotskaya ◽  
Nicolai V. Bovin ◽  
Stanislav V. Pavlovich ◽  
Gennady T. Sukhikh
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Vascular Tone ◽  
Endothelial Activation ◽  
Endothelial Glycocalyx ◽  
Pathogenic Factor ◽  
New Approach ◽  
Pathological Conditions ◽  
Key Factor ◽  
Regulation Of Vascular Tone

Today pre-eclampsia (PE) is considered as a disease of various theories; still all of them agree that endothelial dysfunction is the leading pathogenic factor. Endothelial dysfunction is a sequence of permanent immune activation, resulting in the change of both the phenotype and the functions of an endothelial cell and of the extracellular layer associated with the cell membrane—endothelial glycocalyx (eGC). Numerous studies demonstrate that eGC mediates and regulates the key functions of endothelial cells including regulation of vascular tone and thromboresistance; and these functions are disrupted during PE. Taking into account that eGC and its components undergo alterations under pathological conditions leading to endothelial activation, it is supposed that eGC plays a certain role in pathogenesis of PE. Envisaging the eGC damage as a key factor of PE, might be a new approach to prevention, treatment, and rehabilitation of patients with PE. This approach could include the development of drugs protecting eGC and promoting regeneration of this structure. Since the issue of PE is far from being solved, any effort in this direction might be valuable.

Inhibitor sensitivity of pulmonary vascular carbonic anhydrase

1993 ◽  
Vol 75 (4) ◽  
pp. 1642-1649 ◽  
Author(s):  
T. A. Heming ◽  
C. G. Vanoye ◽  
E. K. Stabenau ◽  
E. D. Roush ◽  
C. A. Fierke ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Carbonic Anhydrase ◽  
Luminal Surface ◽  
Membrane Permeation ◽  
Vascular Activity ◽  
Capillary Endothelial Cells ◽  
Membrane Bound ◽  
Co2 Excretion ◽  
Isolated Rat

The inhibitor sensitivity of pulmonary vascular carbonic anhydrase (CA) was examined in situ to identify the specific isozyme responsible for vascular activity and to study its distribution in the lung. Vascular CA activity was monitored in isolated rat lungs by measuring the rate of CO2 excretion and the magnitude of postcapillary CO2-HCO(3-)-H+ disequilibria. Lungs were perfused with isotonic salines containing gluconate, sulfate, Cl-, or I-, with or without sulfonamide derivatives. Effects of a CA inhibitor purified from porcine blood plasma were also determined. Vascular CA activity was unaffected by gluconate, sulfate, Cl-, and I- (< or = 100 mM). Sulfonamides with vastly different rates of membrane permeation (i.e., readily permeating ethoxzolamide, slowly permeating acetazolamide, and membrane-impermeant quaternary ammonium sulfanilamide) were capable of accessing all vascular CA with similar rates of access. The porcine inhibitor of CA (340 nM) produced a significant, but submaximal, inhibition of vascular CA activity. The data suggest that pulmonary vascular activity reflects a high-activity membrane-bound isozyme, CA IV, which is located on the extracellular luminal surface of capillary endothelial cells.

scholarly journals Effects of Insulin-Like Growth Factor I and II on Prostaglandin Synthesis and Plasminogen Activator Activity in Human Umbilical Vein Endothelial Cells

2005 ◽  
Vol 90 (1) ◽  
pp. 372-378 ◽  
Author(s):  
Fiorella Miceli ◽  
Anna Tropea ◽  
Francesca Minici ◽  
Mariateresa Orlando ◽  
Giuseppina Lamanna ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Colorimetric Assay ◽  
Umbilical Vein ◽  
Vascular Diseases ◽  
Potential Effect ◽  
Human Umbilical Vein ◽  
Cox 2 ◽  
Umbilical Vein Endothelial Cells ◽  
Pai 1

Abstract IGFs seem to contribute to the endothelial dysfunction observed in some vascular diseases. Because locally increased IGFs levels were detected in the preeclamptic fetoplacental unit, we hypothesized their involvement in the dysregulation of fibrinolysis and vascular tone typically observed in the fetoplacental compartment in this pregnancy disease. Therefore, in human umbilical vein endothelial cells (HUVECs), the potential effect of IGFs on the synthesis of plasminogen activators (PAs), PA inibitor-1 (PAI-1), and vasodilator and vasoconstrictor prostaglandins (PGs) was investigated. Moreover, in HUVECs treated with IGFs, the expression of cyclooxygenase (COX)-2, the rate-limiting enzyme in PG synthesis, was evaluated. HUVECs were treated for 24 h with IGFs (1–100 ng/ml) or IL-1β (0.1 ng/ml). PA, PAI-1, and COX-2 mRNA was determined by RT-PCR and PG release and PA activity by RIA and colorimetric assay, respectively. We demonstrated an inhibition of urokinase-type PA activity and a 50% reduction of urokinase-type PA mRNA in HUVECs treated with IGFs. No effect was seen on PAI-1. Finally, both IGFs significantly decreased all PGs tested and COX-2 mRNA, whereas, as expected, IL-1β had an opposite effect. In conclusion, our results suggest for IGFs a potential involvement in the endothelial dysfunction observed in preeclamptic fetoplacental unit.

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