Plasma syndecan-1 concentration as a biomarker for endothelial glycocalyx degradation in septic adult horses.
Abstract: Limited information is available regarding endothelial glycocalyx degradation during sepsis in horses. Plasma syndecan-1 concentrations are increased in consequence of sepsis in other species and have been useful for prognostication. Objective: To determine whether plasma syndecan-1 levels are increased in adult horses affected with sepsis. Methods: Retrospective cohort study. Methods: Adult horses were assigned to one of three groups based on results of physical and laboratory examinations, clinical diagnosis, and results of previously described SIRS classification: Group 1 horses included healthy, nonseptic horses; Group 2 included horses in which clinical illness was identified but that were not considered to be septic; Group 3 included horses with a clinical diagnosis of sepsis. Plasma syndecan-1 concentration was determined in blood obtained at admission into the hospital for each horse, using an equine specific ELISA. Data were analysed using ANOVA and linear regression (p ≤ 0.05). Results: One hundred and ninety-one horses were included and divided into three groups. Scores for SIRS were highest for Group 3 horses and lowest in Groups 1 and 2. Plasma syndecan-1 concentrations in Group 3 horses (50.73 ± 84.24 μg/ml; n = 42) were greater than those for Group 1 (15.69 ± 11.28 μg/ml; n = 66) and Group 2 (16.88 ± 15.30 μg/ml; n = 83). There was no difference regarding syndecan concentrations between Groups 1 and 2. Conclusions: Retrospective study design, solitary time point of measurement for each patient, and lack of a widely accepted consensus regarding definitive diagnosis of sepsis in adult horses. Conclusions: Circulating plasma levels of syndecan-1, a biochemical marker of endothelial glycocalyx damage, are increased in septic adult horses.
© 2022 EVJ Ltd.
Publication Date: 2022-08-05 PubMed ID: 35842924DOI: 10.1111/evj.13862Google Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
The research study explores the use of plasma syndecan-1 levels as an indicator of endothelial glycocalyx degradation in adult horses suffering from sepsis, finding that septic horses had significantly higher syndecan-1 concentrations than healthy or non-septic ill horses.
Study Objective and Methodology
The study aimed to confirm if plasma syndecan-1 levels rise in septic adult horses. This question was prompted by the observed increase in syndecan-1 concentrations in other species experiencing sepsis. Syndecan-1, when found in higher concentrations, is a known biomarker for endothelial glycocalyx degradation, a condition often associated with sepsis.
- The researchers carried out a retrospective cohort study on adult horses.
- The horses were classified into three groups based on physical and laboratory examinations, clinical diagnosis, and previously used SIRS (Systemic Inflammatory Response Syndrome) classifications.
- Group 1 comprised healthy, non-septic horses; Group 2 included horses with identified clinical illness but non-septic; and Group 3 comprised horses with a clinical diagnosis of sepsis.
- The concentration of plasma syndecan-1 in the blood of each horse (collected upon hospital admission) was measured using an equine-specific ELISA (Enzyme-Linked Immunosorbent Assay).
- The researchers then analysed the data using ANOVA (Analysis of Variance) and linear regression tools, with the significance level set at p ≤ 0.05.
Results
- The study included 191 horses, who were divided into the three above-mentioned groups.
- SIRS scores were highest for horses in Group 3 (septic horses) and lowest for horses in Groups 1 (healthy horses) and 2 (non-septic ill horses).
- Plasma syndecan-1 concentrations were significantly higher in Group 3 horses than in Group 1 and Group 2 horses.
- No significant difference was observed in syndecan-1 concentrations between Groups 1 and 2.
Conclusions and Limitations
- The main conclusion of the study is that high circulating plasma levels of syndecan-1, a biochemical indicator of endothelial glycocalyx degradation, are associated with sepsis in adult horses.
- However, this conclusion is limited by factors such as the study’s retrospective design, the single measurement point for each patient, and the absence of a widely accepted standard for definitively diagnosing sepsis in adult horses.
Cite This Article
APA
Hobbs KJ, Johnson PJ, Wiedmeyer CE, Schultz L, Foote CA.
(2022).
Plasma syndecan-1 concentration as a biomarker for endothelial glycocalyx degradation in septic adult horses.
Equine Vet J, 55(3), 456-462.
https://doi.org/10.1111/evj.13862 Publication
Researcher Affiliations
- Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
- Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
- Department of Pathobiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
- Department of Veterinary Medicine and Surgery, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
- Department of Medical Pharmacology and Physiology, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA.
MeSH Terms
- Horses
- Animals
- Syndecan-1 / metabolism
- Retrospective Studies
- Glycocalyx / metabolism
- Sepsis / diagnosis
- Sepsis / veterinary
- Biomarkers
- Horse Diseases / diagnosis
- Horse Diseases / metabolism
Grant Funding
- Animal Health project 1014406 / National Institute of Food and Agriculture
References
This article includes 55 references
- Murphy LS, Wickersham N, McNeil JB, Shaver CM, May AK, Bastarache JA. Endothelial glycocalyx degradation is more severe in patients with non-pulmonary sepsis compared to pulmonary sepsis and associates with risk of ARDS and other organ dysfunction. Ann Intensive Care 2017;7:102-10.
- Lipowsky HH. The endothelial glycocalyx as a barrier to leukocyte adhesion and its mediation by extracellular proteases. Ann Biomed Eng 2012;40:840-8.
- Schmidt EP, Yang Y, Janssen WJ, Gandjeva A, Perez MJ, Barthel L. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat Med 2012;18:1217-23.
- Woodcock TE, Woodcock TM. The revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br J Anaesth 2012;108:384-94.
- Yang Y, Schmidt EP. The endothelial glycocalyx: an important regulator of the pulmonary vascular barrier. Tissue Barriers 2013;1:e23494.
- Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia 2014;69:777-84.
- Florian JA, Kosky JR, Ainslie K, Pang Z, Dull RO, Tarbell JM. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circ Res 2003;93:e136-42.
- Curry FE, Adamson RH. Endothelial glycocalyx: permeability barrier and mechanosensor. Ann Biomed Eng 2012;40:828-39.
- Vincent JL, Nelson DR, Williams MD. Is worsening multiple organ failure the cause of death in patient with severe sepsis?. Crit Care Med 2011;39:1050-5.
- Boisramé-Helms J, Kremer H, Schini-Kerth V, Meziani F. Endothelial dysfunction in sepsis. Curr Vasc Pharmacol 2013;11:150-60.
- Coletta C, Módis K, Oláh G, Brunyánszki A, Herzig DS, Sherwood ER. Endothelial dysfunction is a potential contributor to multiple organ failure and mortality in aged mice subjected to septic shock: preclinical studies in a murine model of cecal ligation and puncture. Crit Care 2014;18:511-3.
- Reitsma S, Slaaf DW, Vink H, Van Zandvoort MA, Oude Egbrink MG. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Arch 2007;454:345-59.
- van Teeffelen JW, Brands J, Stroes ES, Vink H. Endothelial glycocalyx: sweet shield of blood vessels. Trends Cardiovasc Med 2007;17:1101-5.
- van Golen RF, van Gulik TM, Heger M. Mechanistic overview of reactive species-induced degradation of the endothelial glycocalyx during hepatic ischemia/reperfusion injury. Free Radic Biol Med 2012;52(8):1382-402.
- Anand D, Ray S, Srivastava LM, Bhargava S. Evolution of serum hyaluronan and syndecan levels in prognosis of sepsis patients. Clin Biochem 2016;49:768-76.
- Rehm M, Brugger D, Christ F, Conzen P, Thiel M, Jacob M. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation 2007;116:1896-906.
- Nelson A, Berkestedt I, Schimdtchen A, Ljunggren L, Bodelsson M. Increased levels of glycosaminoglycans during septic shock: relation to mortality and the antibacterial action of plasma. Shock 2008;30:623-7.
- Köhler M, Kaufmann I, Briegel J, Jacob M, Goeschl J, Rachinger W. The endothelial glycocalyx degenerates with increasing sepsis severity. Crit Care 2011;15(Suppl 3):P22.
- Sallisalmi M, Tenhunen J, Yang R, Oksala N, Pettilä V. Vascular adhesion protein-1 and syndecan-1 in septic shock. Acta Anaesthesiol Scand 2012;56:316-22.
- Nelson A, Berkestedt I, Bodelsson M. Circulating glycosaminoglycan species in septic shock. Acta Anaesthesiol Scand 2014;58:36-43.
- Puskarich MA, Cornelius DC, Tharp J, Nandi U, Jones AE. Plasma syndecan-1 levels identify a cohort of patients with severe sepsis at high risk for intubation after large-volume intravenous fluid resuscitation. J Crit Care 2016;36:125-9.
- Wei S, Gonzalez Rodriguez E, Chang R, Holcomb JB, Kao LS, Wade CE. Increased syndecan-1 after trauma and risk of sepsis: a secondary analysis of patients from the pragmatic, randomized optimal platelet and plasma ratios (PROPPR) trial. J Am Coll Surg 2018;227:587-95.
- Johansson PI, Stensballe J, Rasmussen LS, Ostrowski SR. A high admission syndecan-1 level, a marker of endothelial glycocalyx degradation, is associated with inflammation, protein C depletion, fibrinolysis, and increased mortality in trauma patients. Ann Surg 2011;254:194-200.
- Holzmann MS, Winkler MS, Strunden MS, Izbicki JR, Schoen G, Greiwe G. Syndecan-1 as a biomarker for sepsis survival after major abdominal surgery. Biomark Med 2018;12:119-27.
- Ikeda M, Matsumoto H, Ogura H, Hirose T, Shimizu K, Yamamoto K. Circulating syndecan-1 predicts the development of disseminated intravascular coagulation in patients with sepsis. J Crit Care 2018;43:48-53.
- Moore JN, Vandenplas ML. Is it the systemic inflammatory response syndrome or endotoxemia in horses with colic?. Vet Clin North Am Equine Pract 2014;30:337-51.
- Roy M-F, Kwong GPS, Lambert J, Massie S, Lockhart S. Prognostic value and development of a scoring system in horses with systemic inflammatory response syndrome. J Vet Intern Med 2017;31:582-92.
- Breuer J, Schusser GF. Erstellung eines Septikämie-Scores für adulte Pferde. Pferdeheilkunde 2012;28:421-8.
- Hatanaka K, Ito T, Madokoro Y, Kamikokuryo C, Niiyama S, Yamada S. Circulating syndecan-1 as a predictor of persistent thrombocytopenia and lethal outcome: a population study of patients with suspected sepsis requiring intensive care. Front Cardiovasc Med 2021;8:730553.
- Black SJ, Lunn DP, Yin C, Hwang M, Lenz SD, Belknap JK. Leukocyte emigration in the early stages of laminitis. Vet Immunol Immunopathol 2006;109:161-6.
- Becker BF, Jacob M, Leipert S, Salmon AHJ, Chappell D. Degradation of the endothelial glycocalyx in clinical settings: searching for the sheddases. Br J Clin Pharmacol 2015;80:389-402.
- Neves FM, Meneses GC, Sousa NE, Menezes RR, Parahyba MC, Martins AM. Syndecan-1 in acute decompensated heart failure-association with renal function and mortality. Circ J 2015;79:1511-9.
- Rahbar E, Cardenas JC, Baimukanova G, Usadi B, Bruhn R, Pati S. Endothelial glycocalyx shedding and vascular permeability in severely injured trauma patients. J Transl Med 2015;13:117-8.
- Naumann DN, Hazeldine J, Davies DJ, Bishop J, Midwinter MJ, Belli A. Endotheliopathy of trauma is an on-scene phenomenon, and is associated with multiple organ dysfunction syndrome: a prospective observational study. Shock 2018;49:420-8.
- Czarnowska E, Karwatowska-Prokopczuk E. Ultrastructural demonstration of endothelial glycocalyx disruption in the reperfused rat heart. Involvement of oxygen free radicals. Basic Res Cardiol 1995;90:357-64.
- Rubio-Gayosso I. Reactive oxygen species mediate modification of glycocalyx during ischemia-reperfusion injury. AJP Heart Circ Physiol 2006;290:H2247-56.
- Schött U, Solomon C, Fries D, Bentzer P. The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review. Scand J Trauma Resus Emerg Med 2016;24:48.
- Koning NJ, Vonk ABA, Vink H, Boer C. Side-by-side alterations in glycocalyx thickness and perfused microvascular density during acute microcirculatory alterations in cardiac surgery. Microcirculation 2016;23:69-74.
- Broekhuizen LN, Lemkes BA, Mooij HL, Meuwese MC, Verberne H, Holleman F. Effect of sulodexide on endothelial glycocalyx and vascular permeability in patients with type 2 diabetes mellitus. Diabetologia 2010;53(12):2646-55.
- Ishikawa K, May CN, Gobe G, Langenberg C, Bellomo R. Pathophysiology of septic acute kidney injury: a different view of tubular injury. Contrib Nephrol 2010;165:18-27.
- Jedlicka J, Becker BF, Chappell D. Endothelial glycocalyx. Crit Care Clin 2020;36:217-32.
- Schmidt EP, Lee WL, Zemans RL, Yamashita C, Downey GP. On, around, and through: neutrophil-endothelial interactions in innate immunity. Physiol (Bethesda, Md) 2011;26:334-47.
- Park PW, Pier GB, Hinkes MT, Bernfield M. Exploitation of syndecan-1 shedding by Pseudomonas aeruginosa enhances virulence. Nature 2001;411:98-102.
- Stepp MA, Gibson HE, Gala PH, Iglesia DDS, Pajoohesh-Ganji A, Pal-Ghosh S. Defects in keratinocyte activation during wound healing in the syndecan-1-deficient mouse. J Cell Sci 2002;115(Pt 23):4517-31.
- Gharbaran R. Advances in the molecular functions of syndecan-1 (SDC1/CD138) in the pathogenesis of malignancies. Crit Rev Oncol Hematol 2015;94:1-17.
- Stepp MA, Pal-Ghosh S, Tadvalkar G, Pajoohesh-Ganji A. Syndecan-1 and its expanding list of contacts. Adv Wound Care 2015;4:235-49.
- Martin JV, Liberati DM, Diebel LN. Excess sodium is deleterious on endothelial and glycocalyx barrier function: a microfluidic study. J Trauma Acute Care Surg 2018;85:128-34.
- Rehm M, Orth V, Kreimeier U, Thiel M, Haller M, Brechtelsbauer H. Changes in intravascular volume during acute normovolemic hemodilution and intraoperative retransfusion in patients with radical hysterectomy. Anesthesiology 2000;92:657-64.
- Chappell D, Bruegger D, Potzel J, Jacob M, Brettner F, Vogeser M. Hypervolemia increases release of atrial natriuretic peptide and shedding of the endothelial glycocalyx. Crit Care 2014;18:538.
- Cerny V, Astapenko D, Brettner F, Benes J, Hyspler R, Lehmann C. Targeting the endothelial glycocalyx in acute critical illness as a challenge for clinical and laboratory medicine. Crit Rev Clin Lab Sci 2017;54:343-57.
- Zhang Y, Wang Z, Liu J, Zhang S, Fei J, Li J. Cell surface-anchored syndecan-1 ameliorates intestinal inflammation and neutrophil transmigration in ulcerative colitis. J Cell Mol Med 2017;21:13-25.
- Floer M, Clausen M, Meister T, Vollenberg R, Bettenworth D, Tepasse P-R. Soluble syndecan-1 as marker of intestinal inflammation: a preliminary study and evaluation of a new panel of biomarkers for non-invasive prediction of active ulcerative colitis. Adv Clin Exp Med 2021;30:655-60.
- Sladden TM, Yerkovich S, Grant M, Zhang F, Liu X, Trotter M. Endothelial glycocalyx shedding predicts donor organ acceptability and is associated with primary graft dysfunction in lung transplant recipients. Transplantation 2019;103:1277-85.
- Dogné S, Flamion B. Endothelial glycocalyx impairment in disease: focus on hyaluronan shedding. Am J Pathol 2020;190:768-80.
- Beurskens DM, Bol ME, Delhaas T, van de Poll MCG, Reutelingsperger CPM, Nicolaes GAF. Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis. Anaesth Intensive Care 2020;48:221-8.
Citations
This article has been cited 0 times.Use Nutrition Calculator
Check if your horse's diet meets their nutrition requirements with our easy-to-use tool Check your horse's diet with our easy-to-use tool
Talk to a Nutritionist
Discuss your horse's feeding plan with our experts over a free phone consultation Discuss your horse's diet over a phone consultation
Submit Diet Evaluation
Get a customized feeding plan for your horse formulated by our equine nutritionists Get a custom feeding plan formulated by our nutritionists