scholarly journals Plasma syndecan-1 and heparan sulfate correlate with microvascular glycocalyx degradation in hemorrhaged rats after different resuscitation fluids

2016 ◽  
Vol 310 (11) ◽  
pp. H1468-H1478 ◽  
Author(s):  
Ivo P. Torres Filho ◽  
Luciana N. Torres ◽  
Christi Salgado ◽  
Michael A. Dubick
Keyword(s):  
Heparan Sulfate ◽  
Plasma Levels ◽  
Blood Chemistry ◽  
Endothelial Glycocalyx ◽  
Total Blood ◽  
Plasma Biomarkers ◽  
Clinical Biomarkers ◽  
Wide Range ◽  
Red Blood Cell Velocity ◽  
Glycocalyx Thickness

The endothelial glycocalyx plays an essential role in many physiological functions and is damaged after hemorrhage. Fluid resuscitation may further change the glycocalyx after an initial hemorrhage-induced degradation. Plasma levels of syndecan-1 and heparan sulfate have been used as indirect markers for glycocalyx degradation, but the extent to which these measures are representative of the events in the microcirculation is unknown. Using hemorrhage and a wide range of resuscitation fluids, we studied quantitatively the relationship between plasma biomarkers and changes in microvascular parameters, including glycocalyx thickness. Rats were bled 40% of total blood volume and resuscitated with seven different fluids (fresh whole blood, blood products, and crystalloids). Intravital microscopy was used to estimate glycocalyx thickness in >270 postcapillary venules from 58 cremaster preparations in 9 animal groups; other microvascular parameters were measured using noninvasive techniques. Systemic physiological parameters and blood chemistry were simultaneously collected. Changes in glycocalyx thickness were negatively correlated with changes in plasma levels of syndecan-1 ( r = −0.937) and heparan sulfate ( r = −0.864). Changes in microvascular permeability were positively correlated with changes in both plasma biomarkers ( r = 0.8, P < 0.05). Syndecan-1 and heparan sulfate were also positively correlated ( r = 0.7, P < 0.05). Except for diameter and permeability, changes in local microcirculatory parameters (red blood cell velocity, blood flow, and wall shear rate) did not correlate with plasma biomarkers or glycocalyx thickness changes. This work provides a quantitative framework supporting plasma syndecan-1 and heparan sulfate as valuable clinical biomarkers of glycocalyx shedding that may be useful in guiding resuscitation strategies following hemorrhage.

scholarly journals Association between plasma glycocalyx component levels and poor prognosis in severe influenza type A (H1N1)

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Xiao Huang ◽  
Feng Lu ◽  
Huanhuan Tian ◽  
Haoran Hu ◽  
Fangyu Ning ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Disease Severity ◽  
Plasma Levels ◽  
Influenza A ◽  
Strong Association ◽  
H1n1 Influenza ◽  
Endothelial Glycocalyx ◽  
Inflammatory Factors ◽  
Severe Influenza ◽  
Influenza A H1n1

AbstractInfluenza A virus infection causes a series of diseases, but the factors associated with disease severity are not fully understood. Disruption of the endothelial glycocalyx contributes to acute lung injury in sepsis, but has not been well studied in H1N1 influenza. We aim to determine whether the plasma glycocalyx components levels are predictive of disease severity in H1N1 influenza. This prospective observational study included 53 patients with influenza A (H1N1) during the influenza season, and 30 healthy controls in our hospital. Patients were grouped by severity and survival. We collected clinical data and blood samples at admission. Inflammatory factors (tumor necrosis factor-α, interleukin-6, interleukin-10) and endothelial glycocalyx components (syndecan-1, hyaluronan, heparan sulfate) were measured. The plasma levels of syndecan-1, hyaluronan, and heparan sulfate were significantly higher in patients with severe influenza A (H1N1) than in mild cases. Syndecan-1 and hyaluronan were positively correlated with disease severity, which was indicated by the APACHE II and SOFA scores and lactate levels, and negatively correlated with albumin levels. At a cutoff point ≥ 173.9 ng/mL, syndecan-1 had a 81.3% sensitivity and 70.3% specificity for predicting of 28-day mortality. Kaplan–Meier analysis demonstrated a strong association between syndecan-1 levels and 28-day mortality (log-rank 11.04, P = 0.001). Elevated plasma levels of syndecan-1 has a potential role in systemic organ dysfunction and may be indicative of disease severity in patients with influenza A (H1N1).

scholarly journals The 3-O-sulfation of heparan sulfate modulates protein binding and lyase degradation

2021 ◽  
Vol 118 (3) ◽  
pp. e2012935118
Author(s):  
Pradeep Chopra ◽  
Apoorva Joshi ◽  
Jiandong Wu ◽  
Weigang Lu ◽  
Tejabhiram Yadavalli ◽  
...  
Keyword(s):  
Heparan Sulfate ◽  
Binding Proteins ◽  
Factor Xa ◽  
Tissue Expression ◽  
Cell Entry ◽  
Synthetic Approach ◽  
Array Technology ◽  
Wide Range ◽  
Simplex Virus

Humans express seven heparan sulfate (HS) 3-O-sulfotransferases that differ in substrate specificity and tissue expression. Although genetic studies have indicated that 3-O-sulfated HS modulates many biological processes, ligand requirements for proteins engaging with HS modified by 3-O-sulfate (3-OS) have been difficult to determine. In particular, the context in which the 3-OS group needs to be presented for binding is largely unknown. We describe herein a modular synthetic approach that can provide structurally diverse HS oligosaccharides with and without 3-OS. The methodology was employed to prepare 27 hexasaccharides that were printed as a glycan microarray to examine ligand requirements of a wide range of HS-binding proteins. The binding selectivity of antithrombin-III (AT-III) compared well with anti-Factor Xa activity supporting robustness of the array technology. Many of the other examined HS-binding proteins required an IdoA2S-GlcNS3S6S sequon for binding but exhibited variable dependence for the 2-OS and 6-OS moieties, and a GlcA or IdoA2S residue neighboring the central GlcNS3S. The HS oligosaccharides were also examined as inhibitors of cell entry by herpes simplex virus type 1, which, surprisingly, showed a lack of dependence of 3-OS, indicating that, instead of glycoprotein D (gD), they competitively bind to gB and gC. The compounds were also used to examine substrate specificities of heparin lyases, which are enzymes used for depolymerization of HS/heparin for sequence determination and production of therapeutic heparins. It was found that cleavage by lyase II is influenced by 3-OS, while digestion by lyase I is only affected by 2-OS. Lyase III exhibited sensitivity to both 3-OS and 2-OS.

scholarly journals Endothelial glycocalyx during early reperfusion in patients undergoing cardiac surgery

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0251747
Author(s):  
Arie Passov ◽  
Alexey Schramko ◽  
Ulla-Stina Salminen ◽  
Juha Aittomäki ◽  
Sture Andersson ◽  
...  
Keyword(s):  
Cardiac Surgery ◽  
Heparan Sulfate ◽  
Coronary Sinus ◽  
Heart Surgery ◽  
Coronary Circulation ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Open Heart Surgery ◽  
Endothelial Glycocalyx ◽  
Early Reperfusion

Background Experimental cardiac ischemia-reperfusion injury causes degradation of the glycocalyx and coronary washout of its components syndecan-1 and heparan sulfate. Systemic elevation of syndecan-1 and heparan sulfate is well described in cardiac surgery. Still, the events during immediate reperfusion after aortic declamping are unknown both in the systemic and in the coronary circulation. Methods In thirty patients undergoing aortic valve replacement, arterial concentrations of syndecan-1 and heparan sulfate were measured immediately before and at one, five and ten minutes after aortic declamping (reperfusion). Parallel blood samples were drawn from the coronary sinus to calculate trans-coronary gradients (coronary sinus–artery). Results Compared with immediately before aortic declamping, arterial syndecan-1 increased by 18% [253.8 (151.6–372.0) ng/ml vs. 299.1 (172.0–713.7) ng/ml, p < 0.001] but arterial heparan sulfate decreased by 14% [148.1 (135.7–161.7) ng/ml vs. 128.0 (119.0–138.2) ng/ml, p < 0.001] at one minute after aortic declamping. There was no coronary washout of syndecan-1 or heparan sulfate during reperfusion. On the contrary, trans-coronary sequestration of syndecan-1 occurred at five [-12.96 ng/ml (-36.38–5.15), p = 0.007] and at ten minutes [-12.37 ng/ml (-31.80–6.62), p = 0.049] after reperfusion. Conclusions Aortic declamping resulted in extracardiac syndecan-1 release and extracardiac heparan sulfate sequestration. Syndecan-1 was sequestered in the coronary circulation during early reperfusion. Glycocalyx has been shown to degrade during cardiac surgery. Besides degradation, glycocalyx has propensity for regeneration. The present results of syndecan-1 and heparan sulfate sequestration may reflect endogenous restoration of the damaged glycocalyx in open heart surgery.

scholarly journals Effects of high-intensity interval training on microvascular glycocalyx and associated microRNAs

2019 ◽  
Vol 316 (6) ◽  
pp. H1538-H1551 ◽  
Author(s):  
Boris Schmitz ◽  
Hannah Niehues ◽  
Malte Lenders ◽  
Lothar Thorwesten ◽  
Andreas Klose ◽  
...  
Keyword(s):  
High Intensity ◽  
Interval Training ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
High Intensity Interval Training ◽  
Sidestream Dark Field ◽  
Sidestream Dark Field Imaging ◽  
High Intensity Interval ◽  
Glycocalyx Thickness

High-intensity interval training (HIIT) has been proposed to exert vasculoprotective effects. This study aimed to evaluate whether HIIT affects the microvasculature, including the endothelial glycocalyx barrier, and to identify associated microRNAs (miRNAs). Fifty healthy participants (23.1 ± 3.0 yr) performed a 4-wk 4 × 30-s all-out running HIIT. Sidestream dark-field imaging was performed at baseline and follow-up to detect changes of the sublingual microvasculature including the endothelial glycocalyx. Exercise parameters were determined by continuous running field test and documentation of high-intensity runs. miRNAs potentially associated with glycocalyx thickness were selected by structured literature search and blood samples for miRNA, and lactate measurements were drawn at baseline and follow-up HIIT. At baseline, a correlation between maximal exercise performance capacity and glycocalyx thickness (determined by perfused boundary region) was detected ( P = 0.045, r = 0.303). Increased exercise performance at follow-up also correlated with glycocalyx thickness ( P = 0.031, r = 0.416), and increased high-intensity sprinting speed was associated with an increased number of perfused vessels ( P = 0.0129, r = 0.449). Literature search identified miR-143, -96-5p, and -24, which were upregulated by HIIT already at baseline and showed an association with peak blood lactate levels after sprints (all P < 0.05). Moreover, increased baseline miR-143 levels predicted increased glycocalyx thickness at follow-up (AUCmiR-143 = 0.92, 95% confidence interval, 0.81–1.0, P = 0.0008). Elevated resting miR-126 levels after the intervention were associated with cell-free versican mRNA levels. We conclude that HIIT induces changes in the endothelial glycocalyx of the microvasculature. Associated miRNAs such as miR-143 may represent a tool for monitoring early vasculoprotective adaptations to physical activity. NEW & NOTEWORTHY High-intensity interval training is known to improve health-related fitness in general and in lifestyle-induced chronic diseases. To visualize microvasculature structure and to detect exercise-induced changes, sublingual sidestream dark-field imaging microscopy was used, and circulating miRNAs were measured. This study shows that exercise-induced changes correlate with associated circulating miRNA, which might be useful for monitoring vasculoprotective effects. Furthermore, sidestream dark-field imaging may represent a sensitive tool for the early detection of exercise-induced systemic vascular changes.

Does a plasma level of chlorpromazine help?

1981 ◽  
Vol 11 (4) ◽  
pp. 729-734 ◽  
Author(s):  
Theodore van Putten ◽  
Philip R. A. May ◽  
Donald J. Jenden
Keyword(s):  
Plasma Level ◽  
Plasma Levels ◽  
Internal Standard ◽  
Gas Chromatography Mass Spectrometry ◽  
Therapeutic Window ◽  
Fixed Dose ◽  
Speed Of Response ◽  
Wide Range ◽  
Dose Period ◽  
Schizophrenic Patients

SynopsisForty-eight newly admitted schizophrenic patients were treated with a fixed, conservative (6·6 mg/kg) dose of chlorpromazine (CPZ) for 28 days. CPZ plasma levels were measured by a gas chromatography mass spectrometry method (GCMS) using 2H6-chlorpromazine as an internal standard. At the end of the fixed-dose period, ‘responders’ had the same plasma levels as ‘non-responders’, suggesting that lack of response is primarily a matter of the illness' sensitivity to CPZ, not to a plasma level below some therapeutic window. After the fixed-dose period, the dosage of CPZ was increased in the ‘non-responders’ by physician's choice. Improvement occurred over a wide range of 10–225 picomoles (3–72 ng)/ml. Above 300 picomoles (95 ng/ml) 4 inaccessible patients eventually became much worse, suggesting psychotoxicity. It is in the inaccessible patient whose illness is only minimally, or not at all, sensitive to CPZ that a plasma level might be especially useful.Interpretation of plasma levels is complicated by the speed of response: some initial non-responders improved by the 56th day of treatment on very conservative plasma levels.

scholarly journals MPO (Myeloperoxidase) Reduces Endothelial Glycocalyx Thickness Dependent on Its Cationic Charge

2018 ◽  
Vol 38 (8) ◽  
pp. 1859-1867 ◽  
Author(s):  
Kashish Manchanda ◽  
Hana Kolarova ◽  
Christina Kerkenpaß ◽  
Martin Mollenhauer ◽  
Jan Vitecek ◽  
...  
Keyword(s):  
Endothelial Glycocalyx ◽  
Glycocalyx Thickness

Abstract 3476: Higher plasma levels of heparan sulfate are associated with improved survival of patients with advanced ovarian cancer.

2013 ◽  
Author(s):  
Matthew S. Block ◽  
Matthew J. Maurer ◽  
Krista M. Goergen ◽  
Courtney L. Erskine ◽  
Marshall D. Behrens ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Heparan Sulfate ◽  
Plasma Levels ◽  
Advanced Ovarian Cancer

Utilization of amino acids by pre-ruminant lambs. III.* The influence of age and the dietary proportions of essential and non-essential amino acids on the levels of urea, ammonia and free amino acids in the blood plasma of milk-fed lambs

1978 ◽  
Vol 29 (1) ◽  
pp. 145 ◽  
Author(s):  
H Dove
Keyword(s):  
Amino Acids ◽  
Plasma Levels ◽  
Free Amino Acids ◽  
Free Amino ◽  
Essential Amino Acids ◽  
High Plasma ◽  
Whole Milk ◽  
Wide Range ◽  
Pattern Characteristic ◽  
Pre Treatment

Jugular blood samples were obtained from 10.5 kg and 28 kg lambs receiving a diet of reconstituted cows' whole milk. The lambs were then given diets in which the proportion of essential amino acids (BAA) in the dietary crude protein was altered over a wide range. A second blood sample was taken after lambs had received such diets for 12 days. Plasma obtained from these samples was analysed for free amino acids, urea and ammonia. The pattern of plasma free amino acids (PFAA) in lambs given reconstituted cows' whole milk is described. In both the pre-treatment and post-treatment samples, the heavier lambs appeared to have lower plasma levels of all EAA, and high plasma levels of glycine, serine, urea and ammonia. In the lighter lambs, there were pronounced responses of PFAA levels to changes in the dietary proportion of EAA. At low proportions, the levels of most EAA in plasma were low. Lysine and phenylalanine were exceptions. In addition, levels of many non-essential amino acids (non-EAA), particularly serine and glycine, were high. At high proportions of EAA, plasma levels of all EAA, especially methionine, rose markedly. Within the non-EAA, serine, proline and glycine were reduced, while taurine and cystathionine increased. In the plasma of the heavier lambs, the response of some amino acids to a given dietary change differed from the response in the lighter lambs. This was especially true of methionine, tyrosine, phenylalanine and arginine. There was also marked between-animal variation in plasma levels. When expressed as molar proportions of total PFAA, results were similar to those of the lighter lambs. There was a pronounced similarity between the response of the PFAA to diets with a low proportion of EAA, and the PFAA pattern characteristic of developing kwashiorkor. __________________ *Part II, Aust. J. Agric. Res., 28, 933 (1977).

Effect of Continuous Supression of Heparan Sulfate on Arterial Endothelial Alignment and Gene Expression Under Several Shear Stress Waveforms

2010 ◽  
Author(s):  
Charles S. Wallace ◽  
Morton H. Friedman
Keyword(s):  
Gene Expression ◽  
Shear Stress ◽  
Heparan Sulfate ◽  
G Proteins ◽  
Carotid Arteries ◽  
Sialic Acids ◽  
Endothelial Glycocalyx ◽  
Luminal Surface ◽  
Gel Layer ◽  
Junction Proteins

The literature suggests that endothelial cells (ECs) possess many molecules that have mechanosensor capabilities, such as intracellular junction proteins, G proteins, ion channels, integrins, and the glycocalyx [1]. The endothelial glycocalyx is located on the luminal surface of ECs and interacts with the passing blood, thus making it a strong mechanosensor candidate. The glycocalyx is a negatively charged gel layer ranging from 0.5 μm thick in capillaries to 4.5 μm thick in carotid arteries [2]. The glycocalyx consists primarily of sialic acids, chondroitin sulfate, hyaluronic acid, and heparan sulfate (HS). HS is the most abundant glycosaminoglycan within the glycocalyx, and it is one of the most studied molecules in this layer [3].

scholarly journals Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis

2020 ◽  
Vol 48 (3) ◽  
pp. 221-228
Author(s):  
Daniëlle MH Beurskens ◽  
Martine E Bol ◽  
Tammo Delhaas ◽  
Marcel CG van de Poll ◽  
Chris PM Reutelingsperger ◽  
...  
Keyword(s):  
Organ Failure ◽  
Early Stage ◽  
Characteristic Curve ◽  
Area Under The Curve ◽  
Dark Field ◽  
Endothelial Glycocalyx ◽  
Pathophysiological Mechanism ◽  
Heparin Binding ◽  
Sidestream Dark Field ◽  
Glycocalyx Thickness

Microcirculatory alterations play an important role in the early phase of sepsis. Shedding of the endothelial glycocalyx is regarded as a central pathophysiological mechanism causing microvascular dysfunction, contributing to multiple organ failure and death in sepsis. The objective of this study was to investigate whether endothelial glycocalyx thickness at an early stage in septic patients relates to clinical outcome. We measured the perfused boundary region (PBR), which is inversely proportional to glycocalyx thickness, of sublingual microvessels (5–25 µm) using sidestream dark field imaging. The PBR in 21 patients with sepsis was measured within 24 h of admission to the intensive care unit (ICU). In addition, we determined plasma markers of microcirculatory dysfunction and studied their correlation with PBR and mortality. Endothelial glycocalyx thickness in sepsis was significantly lower for non-survivors as compared with survivors, indicated by a higher PBR of 1.97 [1.85, 2.19]µm compared with 1.76 [1.59, 1.97] µm, P=0.03. Admission PBR was associated with hospital mortality with an area under the curve of 0.778 based on the receiver operating characteristic curve. Furthermore, PBR correlated positively with angiopoietin-2 (rho=0.532, P=0.03), indicative of impaired barrier function. PBR did not correlate with Acute Physiology and Chronic Health Evaluation IV (APACHE IV), Sequential Organ Failure Assessment score (SOFA score), lactate, syndecan-1, angiopoietin-1 or heparin-binding protein. An increased PBR within the first 24 h after ICU admission is associated with mortality in sepsis. Further research should be aimed at the pathophysiological importance of glycocalyx shedding in the development of multi-organ failure and at therapies attempting to preserve glycocalyx integrity.

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