Evolution of serum hyaluronan and syndecan levels in prognosis of sepsis patients

Anand, Dimple; Ray, Sumit; Srivastava, Lalit M.; Bhargava, Seema

doi:10.1016/j.clinbiochem.2016.02.014

Cited by 99 publications

(116 citation statements)

References 22 publications

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“…MMPs are thought to be some of the key enzymes responsible for the shedding of the EG in a variety of diseases ranging from diabetes to inflammatory conditions 49,93,113,122,123 . Syndecan‐1, HS, CS, and HA are all considered valid markers of EG integrity and applied in both experimental and clinical research to identify EG shedding 18,120,124‐126 …”

Section: Normal Structure and Function Of The Endothelial Glycocalyxmentioning

confidence: 99%

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The endothelial glycocalyx: Structure and function in health and critical illness

Gaudette

Hughes

Boller

2020

J Vet Emergen Crit Care

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Objective To conduct a narrative review of the current literature in reference to the structure and function of the endothelial glycocalyx (EG) and its contribution to the pathophysiology of conditions relevant to the veterinary emergency and critical care clinician. Novel therapies for restoring or preserving the EG will also be discussed. Data Sources Online databases (PubMed, CAB abstracts, Scopus) were searched between January 1st 2017 and May 1st 2017 for English language articles without publication date restriction. Keywords included EG, endothelial surface layer, degradation, syndecan‐1, heparan sulfate, critical illness, sepsis, trauma, and therapeutics. Data Synthesis The EG is a complex and important structure located on the luminal surface of all blood vessels throughout the body. It plays an important role in normal vascular homeostasis including control of fluid exchange across the vascular barrier. Loss or degradation of the EG has an impact on inflammation, coagulation, and vascular permeability and tone. These changes are essential components in the pathophysiology of many conditions including sepsis and trauma. A substantial body of experimental animal and human clinical research over the last decade has demonstrated increased circulating concentrations of EG degradation products in these conditions. However, veterinary‐specific research into the EG and critical illness is currently lacking. The utility of EG degradation products as diagnostic and prognostic tools continues to be investigated and new therapies to preserve or improve EG structure and function are under development. Conclusions The recognition of the presence of the EG has changed our understanding of transvascular fluid flux and the pathophysiology of many conditions of critical illness. The EG is an exciting target for novel therapeutics to improve morbidity and mortality in conditions such as sepsis and trauma.

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Section: Normal Structure and Function Of The Endothelial Glycocalyxmentioning

confidence: 99%

“…An increase in circulating biomarkers of EG degradation, such as SDC1, HS, and HA, occurs in animals and people with SIRS or sepsis 18,117,126,128,136‐139 . IM has allowed for the direct visualization of EG reduction in people with sepsis 5,54 .…”

Section: Disease States Leading To Glycocalyx Dysfunctionmentioning

confidence: 99%

The endothelial glycocalyx: Structure and function in health and critical illness

Gaudette

Hughes

Boller

2020

J Vet Emergen Crit Care

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“…Serum heparan sulfate level has been shown to be elevated 301 in sepsis (80). Serum hyaluronan, syndecan were also shown to be decreased in sepsis (81). Nelson 302 et al showed increased glycosaminoglycans (GAG) in septic shock and related this to endothelial 303 damage (82).…”

Section: Warburg Common Pathogenesis Model In Sepsis (Figure 2): 173mentioning

confidence: 99%

“…Decreased hyaluronan and syndecan which are components of the endothelial 616 glycocalyx were shown to be decreased in sepsis (81) and heparan sulfate levels are elevated in 617 sepsis shows endothelial glycalyx may be degraded in sepsis leading to endothelial dysfunction 618 (80). As discussed earlier( Figure 5), endothelial glycocalyx degradation may trigger phenotype 619 change and decreased in ascorbic acid level plays a crucial role in it.…”

Section: Respiratory Dysfunction In Sepsis Ards Andmentioning

confidence: 99%

Fundamental role of Warburg effect in various pathophysiological processes

Natesan¹

2017

Preprint

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Even though high NO via iNOS was involved in most of the pathologies including sepsis, any 56 substance that inhibits or uncouples the mitochondrial respiration can initiate this Warburg effect 57 and irreversible dedifferentiation. A mild and reversible Warburg differentiation dedifferentiation 58 effect may be necessary for normal functioning and the same effect in exaggerated and irreversible 59 way leading to irreversible dedifferentiation states may be the underlying mechanism in most of the 60 diseases including septic shock. 61 62 Keywords: Septic shock, Warburg effect, dedifferentiation, differentiation therapy, ascorbic acid, 63 adrenergic blockers, glycolysis. 64Abbreviations : systemic hypertension(SHT), pulmonary arterial hypertension (PAH),congestive 65 heart failure (CHF), acute kidney injury(AKI),acute respiratory distress syndrome(ARDS),diabetes 66 mellitus(DM),inducible nitric oxide synthase (iNOS) . 67 68 69 70 INTRODUCTION: 71This review article tries to show the fundamental role played by Warburg effect in most of the 72 pathologies. Warburg common pathogenesis model is proposed to show the common underlying 73 mechanism in most of the pathologies and septic shock was used as the base model. 74Sepsis is the harmful systemic response of the host to the infection (1). According to Lewis Thomas 75 the host's response to pathogen is more detrimental than the pathogen itself (2). Septic shock and 76 severe sepsis associated multi-organ dysfunction carries high mortality rate ~ 40 -70% (3,4). 77Septic shock is refractory to the vasopressors in most of the cases; this includes norepinephrine, the 78 primary drug used in reviving blood pressure in septic shock. Vascular hypo reactivity to various 79 vasopressors in septic shock has been studied extensively, many reviews are available (5,86). 80Irrespective of advances in this field, exact underlying mechanism behind septic shock is still a 81 mystery. Post mortem studies couldn't find the underlying cause in most of the cases, surprisingly 82 most of the organs looked normal (6).Lot of treatment options which were successful in animal 83 models were failed to show benefit in human studies, ranging from Nitric oxide Synthase (NOS) 84Inhibitors, Cyclooxygenase (COX) Inhibitors, endotoxin neutralizing proteins, TNF alpha 85 antagonists etc.., (3). Some of the recent promising directions include, counterintuitive use of 86 antihypertensive in septic shock -alpha2 adrenergic receptor agonists -clonidine (7-9), beta 87 blockers reviewed in (10, 11) -aimed to reduce the sympathetic hyper activation and hyper 88 metabolism associated with sepsis. Alpha2 AR antagonist also has been shown to improve survival 89 in sepsis animal model (12). Vitamin C has been used in sepsis reviewed in (13), Glycolysis 90 inhibitor shikonin (14), cytochrome C (15) and Caffeine (16). 91 Warburg common pathogenesis model has been proposed in this review article to explain the role of 92Warburg effect in most of the pathologies using septic shock as the base model. The model was 9...

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“…As yet, there are very few studies reported (many in animal models of sepsis) on these biomarkers and their role in management of sepsis and its resultant hypotension and organ failure. In the study under consideration [10], the abstract of which is reproduced above, the importance of serial estimations of these markers has been emphasized.…”

Section: Commentarymentioning

confidence: 99%

Glycocalyx Components in Prognosis of Sepsis - A Commentary

Bhargava¹,

Anand²,

S³

et al. 2017

Immunotherapy

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Objectives: Endothelial glycocalyx shedding has been recognized as a contributor in sepsis pathophysiology. Hence, we attempted to analyse hyaluronan and syndecan (glycocalyx components) as markers of morbidity and prognosis of sepsis by performing serial measurements in these patients. Design and methods:Subjects were community acquired sepsis, severe sepsis and septic shock patients (150) admitted to ICU of our tertiary care hospital and controls were 50 healthy volunteers. Serum concentrations of markers were measured on days 1,3,5,7 of ICU admission. Survival was assessed after 90 days. Statistical analysis was performed by SPSS version 17.Results: Hyaluronan and syndecan levels were significantly elevated in all categories of sepsis patients as compared to controls (p<0.001). Levels of both markers were increased in severe sepsis and septic shock patients as compared to sepsis patient group at all-time points. Hyaluronan and syndecan differentiated survivors from non survivors (p<0.001). Unlike non-survivors, in the survivor group, median hyaluronan and syndecan levels decreased significantly (p<0.001) in subsequent measurements. ROC analysis for the prediction of mortality identified cut-offs of 441 ng/ml and 898 ng/ml for hyaluronan and syndecan, respectively. The specificity and negative predictive values were 90% and 90% for hyaluronan and 86% and 91% for syndecan, respectively. Kaplan Meier curves revealed similar results. Both markers correlated significantly with APACHE II and SOFA scores. Conclusion:These observations indicate that serial measurements of hyaluronan and syndecan are significant prognostic markers for morbidity and survival in sepsis. Further, therapeutic interventional possibilities need to be explored in experimental interventional prospective multi-centre trials.

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Evolution of serum hyaluronan and syndecan levels in prognosis of sepsis patients

Cited by 99 publications

References 22 publications

The endothelial glycocalyx: Structure and function in health and critical illness

The endothelial glycocalyx: Structure and function in health and critical illness

Fundamental role of Warburg effect in various pathophysiological processes

Glycocalyx Components in Prognosis of Sepsis - A Commentary

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