Sepsis-induced damage to endothelial glycocalyx (literature review)
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endothelial glycocalyx
septic shock
glycocalyx shedding
vascular permeability

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Ilyina YY, Fot EV, Kuzkov VV, Kirov MY Sepsis-induced damage to endothelial glycocalyx (literature review). Annals of Critical Care. 2019;(2):32–39. doi:10.21320/1818-474X-2019-2-32-39.


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Glycocalyx is a gel-like layer covering the surface of vascular endothelial cells. It consists of membrane-attached proteoglycans, glycosaminoglycan chains, glycoproteins, and plasma adhesive proteins. Glycocalyx plays a key role in maintaining vascular homeostasis, controls vascular permeability and the tone of the microvasculature, prevents microvascular thrombosis and regulates leukocyte adhesion. In sepsis and septic shock, damage and shedding of glycocalyx occurs. The degradation of glycocalyx is activated by reactive oxygen species and pro-inflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin-1β (IL-1β). The inflammation-mediated degradation of glycocalyx leads to vascular hyperpermeability, unregulated vasodilation, microvascular thrombosis, and enhanced leukocyte adhesion. The inflammation-mediated degradation of glycocalyx leads to vascular hyperpermeability, unregulated vasodilation, microvascular thrombosis, and enhanced leukocyte adhesion. Clinical studies have demonstrated a correlation between the levels of glycocalyx components in the blood and organ dysfunction and mortality in sepsis and septic shock. Inflammation-induced damage to glycocalyx can cause a number of specific clinical effects of sepsis, including acute kidney damage, respiratory failure and liver dysfunction. Infusion therapy is an integral part of the treatment of sepsis, but super-aggressive infusion load methods (leading to hypervolemia) may increase the degradation of glycocalyx. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan 1 or heparan sulfate, can be used as markers of endothelial dysfunction and sepsis severity.
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  1. Uchimido R., Schmidt E.P., Shapiro N.I. The glycocalyx: a novel diagnostic and therapeutic target in sepsis. Crit. Care. 2019; 23: 16. DOI: 10.1186/s13054-018-2292-6
  2. Colbert J.F., Schmidt E.P. Endothelial and microcirculatory function and dysfunction in sepsis. Clin. Chest. Med. 2016; 37: 263–275. DOI: 10.1016/j.ccm.2016.01.009
  3. Максименко А.В. Эндотелиальный гликокаликс — значимая составная часть двойного защитного слоя сосудистой стенки: диагностический индикатор и терапевтическая мишень. Кардиологический вестник. 2016; 11(3): 94–100. [Maksimenko A.V. endothelial glygogalyx is significant constitutive part of double protective layer into vascular wall: diagnostic index and therapeutic target. Kardiologicheskij Vestnik. 2016; 11(3): 94–100. (In Russ)]
  4. Гончар И.В., Балашов С.А.,. Валиев И.А., Мелькумянц А.М. Роль эндотелиального гликокаликса в механогенной регуляции тонуса артериальных сосудов. Труды московского физико-химического института. 2017; 1: 101–108. [Gonchar I.V., Balashov S.A., Valiev I.A., Melkumyanz А.М. The role of endothelial glycocalyx in the mechanogenic regulation of arterial vascular tone. Proceedings of the Moscow Institute of Physics and Chemistry. 2017; 1: 101–108. (In Russ)]
  5. Woodcock T.E., Woodcock T.M. Revised Starling equation and the glycocalyx model of transvascular fluid exchange: an improved paradigm for prescribing intravenous fluid therapy. Br. J. Anaesth. 2012; 108: 384–394. DOI: 10.1093/bja/aer515
  6. Frati-Munari A.C. Medical significance of endothelial glycocalyx. Arch Cardiol Mex. 2013; 83: 303–312. DOI: 10.1016/j.acmx.2013.04.015
  7. Kolářová H., Ambrůzová B., Svihálková L., et al. Modulation of endothelial glycocalyx structure under inflammatory conditions. Mediators Inflamm. 2014: ID 694312. DOI: 10.1155/2014/694312
  8. Singh A., Ramnath R.D., Foster R.R., et al. Reactive oxygen species modulate the barrier function of the human glomerular endothelial glycocalyx. PLoS One. 2013; 8(1): e55852. DOI: 10.1371/journal.pone.0055852
  9. Stehouwer C.D., Smulders YM. Microalbuminuria and risk for cardiovascular disease: analysis of potential mechanisms. J. Am. Soc. Nephrol. 2006; 17: 2106–2111. DOI: 10.1681/ASN.2005121288
  10. Forbes J.M., Coughlan M.T., Cooper ME. Oxidative stress as a major culprit in kidney disease in diabetes. Diabetes. 2008; 57: 1446–1454. DOI: 10.2337/db08–0057
  11. Adachi T., Fukushima T., Usami Y., et al. Binding of human xanthine oxidase to sulphated glycosaminoglycans on the endothelial-cell surface. Biochem J. 1993; 289: 523–527. DOI: 10.1042/bj2890523
  12. Becker M., Menger M.D., Lehr H.A. Heparin-released superoxide dismutase inhibits postischemic leukocyte adhesion to venular endothelium. Am. J. Physiol. 1994; 267: 925–930. DOI: 10.1152/ajpheart.1994.267.3.H925
  13. Becker B.F., Chappell D., Bruegger D., et al. Therapeutic strategies targeting the endothelial glycocalyx: acute deficits, but great potential. Cardiovasc. Res. 2010; 87: 300–310. DOI: 10.1093/cvr/cvq137
  14. Gouverneur M., Spaan J.A., Pannekoek H., et al. Fluid shear stress stimulates incorporation of hyaluronan into endothelial cell glycocalyx. American Journal of Physiology. Heart and Circulatory Physiology. 2006; 290: 458–462. DOI: 10.1152/ajpheart.00592.2005
  15. Johansson P.I., Henriksen H.H., Stensballe J., et al. Traumatic endotheliopathy: a prospective observational study of 424 severely injured patients. Ann. Surg. 2017; 265(3): 597–603. DOI: 10.1097/SLA.0000000000001751
  16. Gandhi N.S., Mancera R.L. The structure of glycosaminoglycans and their interactions with proteins. Chem. Biol. Drug. Des. 2008; 72(6): 455–482. DOI: 10.1111/j.1747-0285.2008.00741.x
  17. Paulus P., Jennewein C., Zacharowski K. Biomarkers of endothelial dysfunction: can they help us deciphering systemic inflammation and sepsis? Biomarkers. 2011; 16: 11–21. DOI: 10.3109/1354750X.2011.587893
  18. Reitsma S., Slaaf D.W., Vink H., et al. The endothelial glycocalyx: composition, functions, and visualization. Pflugers Archiv: European Journal of Physiology. 2007; 454: 345–359. DOI: 10.1007/s00424-007-0212-8
  19. Rehm M., Bruegger D., Christ F., et al. Shedding of the endothelial glycocalyx in patients undergoing major vascular surgery with global and regional ischemia. Circulation. 2007; 116: 1896–1906. DOI: 10.1161/circulationaha.106.684852
  20. Burke-Gaffney A., Evans T.W. Lest we forget the endothelial glycocalyx in sepsis. Crit. Care. 2012; 16: 121. DOI: 10.1186/cc11239
  21. Kozar R.A., Peng Z., Zhang R., et al. Plasma restoration of endothelial glycocalyx in a rodent model of hemorrhagic shock. Anesth. Analg. 2011; 112: 1289–1295. DOI: 10.1213/ANE.0b013e318210385c
  22. Cancel L.M., Ebong E.E., Mensah S., et al. Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model. Atherosclerosis. 2016; 252: 136–146. DOI: 10.1016/j.atherosclerosis.2016.07.930
  23. Miranda C.H., de Carvalho Borges M., Schmidt A., et al. Evaluation of the endothelial glycocalyx damage in patients with acute coronary syndrome Atherosclerosis. 2016; 247: 184–188. DOI: 10.1016/j.atherosclerosis.2016.02.023
  24. Padberg J.S., Wiesinger A., di Marco G.S. Damage of the endothelial glycocalyx in chronic kidney disease. Atherosclerosis. 2014; 234: 335–343. DOI: 10.1016/j.atherosclerosis.2014.03.016
  25. Nieuwdorp M., Mooij H.L., Kroon J., et al. Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. Diabetes. 2006; 55: 1127–1132. DOI: 10.2337/diabetes.55.04.06.db05–1619
  26. Jacob M., Saller T., Chappell D., et al. Physiological levels of A-, B- and C-type natriuretic peptide shed the endothelial glycocalyx and enhance vascular permeability. Basic Res Cardiol. 2013; 108: 347. DOI: 10.1007/s00395-013-0347-z
  27. Salmon A.H., Satchell S.C. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J. Pathol. 2012; 226: 562–574. DOI: 10.1002/path.3964
  28. Myburgh J.A., Mythen M.G. Resuscitation fluids. N. Engl. J. Med.. 2013; 369: 1243–1251.
  29. Henrich M., Gruss M., Weigand M.A. Sepsis-induced degradation of endothelial glycocalyx. Sci World J. 2010; 10: 917–923. DOI: 10.1100/tsw.2010.88
  30. Bruegger D., Jacob M., Rehm M. Atrial natriuretic peptide induces shedding of the endothelial glycocalyx in the coronary vascular bed of guinea pig. Am. J. Physiol. Heart Circ. Physiol. 2005; 289: 1993–1999. DOI: 10.1152/ajpheart.00218.2005
  31. Adamson R.H., Lenz J.F., Zhang X., et al. Oncotic pressures opposing filtration across non-fenestrated rat microvessels. Journal of Physiology. 2004; 557: 889–907. DOI: 10.1113/jphysiol.2003.058255
  32. Levick J.R., Michel C.C. Microvascular fluid exchange and the revised Starling principle. Cardiovascular Research. 2010; 87: 198–210. DOI: 10.1093/cvr/cvq062
  33. Ait-Oufella H., Maury E., Lehoux S., et al. The endothelium: physiological functions and role in microcirculatory failure during severe sepsis. Intensive Care Medicine. 2010; 36: 1286–1298. DOI: 10.1007/s00134-010-1893-6
  34. Pries A.R., Secomb T.W., Gaehtgens P. The endothelial surface layer. Pflugers Arch. 2000; 440: 653–666. DOI: 10.1007/s004240000307
  35. Jacob M., Bruegger D., Rehm M., et al. The endothelial glycocalyx affords compatibility of Starlingʼs principle and high cardiac interstitial albumin levels. Cardiovascular Research. 2007; 73: 575–586. DOI: 10.1016/j.cardiores.2006.11.021
  36. Florian J.A., Kosky J.R., Ainslie K., et al. Heparan sulfate proteoglycan is a mechanosensor on endothelial cells. Circ. Res. 2003; 93: 136–142. DOI: 10.1161/01.RES.0000101744.47866.D5
  37. Chelazzi C., Villa G., Mancinelli P., et al. Glycocalyx and sepsis-induced alterations in vascular permeability. Crit. Care. 2015; 19: 26. DOI: 10.1186/s13054-015-0741-z
  38. Karamysheva A.F. Mechanisms of angiogenesis. Biochemistry. 2008; 73: 751–762.
  39. Becker B.F., Jacob M., Leipert S., et al. Degradation ot the endothelial glycocalyx in clinical settings: searching for the sheddases. Br. J. Clin Pharmacol. 2015; 80: 389–402. DOI: 10.1111/bcp.12629
  40. Moseley R., Waddington R.J., Embery G. Degradation of glycosaminoglycans by reactive oxygen species derived from stimulated polymorphonuclear leukocytes. Biochim. Biophys. Acta. 1997; 1362: 221. DOI: 10.1016/S0925–4439(97)00083–5
  41. Weinbaum S., Tarbell J.M., Damiano E.R. The structure and function of the endothelial glycocalyx layer. Annu Rev. Biomed. Eng. 2007; 9: 121–167. DOI: 10.1146/annurev.bioeng.9.060906.151959
  42. Forni M., Mazzola S., Ribeiro L.A., et al. Expression of endothelin-1 system in a pig model of endotoxic shock. Regul. Pept. 2005; 131: 89–96. DOI: 10.1016/j.regpep.2005.07.001
  43. Johansson P., Stensballe J., Ostrowski S. Shock induced endotheliopathy (SHINE) in acute critical illness — a unifying pathophysiologic mechanism. Crit. Care. 2017; 21: 25. DOI: 10.1186/s13054-017-1605-5
  44. Johansson P.I., Stensballe J., Rasmussen L.S., et al. 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. DOI: 10.1097/SLA.0b013e318226113d
  45. Steppan J., Hofer S., Funke B. Sepsis and major abdominal surgery lead to flaking of the endothelial glycocalyx. J. Surg. Res. 2011; 165: 136–141. DOI: 10.1016/j.jss.2009.04.034
  46. Ostrowski S.R., Gaïni S., Pedersen C.J., et al. Sympathoadrenal activation and endothelial damage in patients with varying degrees of acute infectious disease: An observational study. Crit. Care. 2015; 30: 90–96. DOI: 10.1016/j.jcrc.2014.10.006
  47. Haywood-Watson R.J., Holcomb J.B., Gonzalez E.A., et al. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011; 6 (8): e23530. DOI: 10.1371/journal.pone.0023530
  48. Aird W.C. Endothelial cell heterogeneity. Cold Spring Harb Perspect Med. 2012; 2: a006429. DOI: 10.1101/cshperspect.a006429
  49. Ince C., Mayeux P.R., Nguyen T. The endothelium in sepsis shock. Shock. 2016; 45(3): 259–270. DOI: 10.1097/SHK.0000000000000473
  50. Zeng Y., Adamson R.H., Curry F.R.E., et al. Sphingosine-1-phosphate protects endothelial glycocalyx by inhibiting syndecan-1 shedding. Am. J. Physiol. Heart Circ. Physiol. 2014; 306: H363–H372. DOI: 10.1152/ajpheart.00687.2013
  51. Coldewey S. M, Benetti E., Collino M., et al. Elevation of serum sphingosine-1-phosphate attenuates impaired cardiac function in experimental sepsis. Sci Rep. 2016; 6: 27594. DOI: 10.1038/srep27594.
  52. Schmidt E.P, Yang Y., Janssen W.J., et al. The pulmonary endothelial glycocalyx regulates neutrophil adhesion and lung injury during experimental sepsis. Nat. Med. 2012; 18: 1217–1223. DOI: 10.1038/nm.2843
  53. Purushothaman A., Chen L., Yang Y., et al. Heparanase stimulation of protease expression implicates it as a master regulator of the aggressive tumor phenotype in myeloma. J. Biol. Chem. 2008; 283: 32628–32636. DOI: 10.1074/jbc.M806266200
  54. Masola V., Onisto M., Zaza G., et al. A new mechanism of action of sulodexide in diabetic nephropathy: inhibits heparanase-1 and prevents FGF-2-induced renal epithelial-mesenchymal transition. J. Transl. Med. 2012; 10: 213. DOI: 10.1186/1479-5876-10-213
  55. Song J.W., Zullo J.A., Liveris D., et al. Therapeutic restoration of endothelial glycocalyx in sepsis. J. Pharmacol. Exp. Ther. 2017; 361: 115–121. DOI: 10.1124/jpet.116.239509
  56. Yang Y., Haeger S.M., Suflita M.A., et al. Fibroblast growth factor signaling mediates pulmonary endothelial glycocalyx reconstitution. Am. J. Respir. Cell Mol. Biol. 2017; 56: 727–737. DOI: 10.1165/rcmb.2016–0338OC
  57. Rizzo A. N, Dudek S.M. Endothelial glycocalyx repair: building a wall to protect the lung during sepsis. Am. J. Respir. Cell Mol. Biol. 2017; 56: 687–688. DOI: 10.1165/rcmb.2017–0065ED
  58. Frati-Munari A.C. Medical significance of endothelial glycocalyx. Arch. Cardiol. Mex. 2013; 83: 303–312. DOI: 10.1016/j.acmx.2013.04.015
  59. Nieuwdorp M., van Haeften T.W., Gouverneur M.C., et al. Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo. Diabetes. 2006; 55: 480–486. DOI: 10.2337/diabetes.55.02.06.db05-1103
  60. Bruegger D., Schwartz L., Chappell D., et al. Release of atrial natriuretic peptide precedes shedding of the endothelial glycocalyx equally in patients undergoing on- and off-pump coronary artery bypass surgery. Basic Res. Cardiol. 2011; 106: 1111–1121.
  61. Adamson R.H., Clark J.F., Radeva M., et al. Albumin modulates S1P delivery from red blood cells in perfused microvessels: mechanism of the protein effect. Am. J. Physiol. Heart Circ. Physiol. 2014; 306: 1011–1017. DOI: 10.1152/ajpheart.00829.2013
  62. Jacob M., Bruegger D., Rehm M., et al.Contrasting effects of colloid and crystalloid resuscitation fluids on cardiac vascular permeability. Anesthesiology. 2006; 104: 1223–1231.
  63. Jacob M., Paul O., Mehringer L., et al. Albumin augmentation improves condition of guinea pig hearts after 4 hr of cold ischemia. Transplantation. 2009; 87: 956–965. DOI: 10.1097/TP.0b013e31819c83b5
  64. Torres L.N., Sondeen J.L., Ji L., et al. Evaluation of resuscitation fluids on endothelial glycocalyx, venular blood flow, and coagulation function after hemorrhagic shock in rats. J. Trauma Acute Care Surg. 2013; 75: 759–766. DOI: 10.1097/TA.0b013e3182a92514
  65. Peng Z., Pati S., Potter D., et al. Fresh frozen plasma lessens pulmonary endothelial inflammation and hyperpermeability after hemorrhagic shock and is associated with loss of syndecan 1. Shock. 2013; 40: 195–202. DOI: 10.1097/SHK.0b013e31829f91fc
  66. Haywood-Watson R.J., Holcomb J.B., Gonzalez E.A., et al. Modulation of syndecan-1 shedding after hemorrhagic shock and resuscitation. PLoS One. 2011; 6: e23530. DOI: 10.1371/journal.pone.0023530
  67. Straat M., Müller M.C., Meijers J.C., et al. Effect of transfusion of fresh frozen plasma on parameters of endothelial condition and inflammatory status in non-bleeding critically ill patients: a prospective substudy of a randomized trial. Crit. Care. 2015; 19: 62–67. DOI: 10.1186/s13054-015-0828-6
  68. Chappell D., Hofmann-Kiefer K., Jacob M., et al. TNF-alpha induced shedding of the endothelial glycocalyx is prevented by hydrocortisone and antithrombin. Basic Res. Cardiol. 2009; 104: 78–89.
  69. De Backer D., Creteur J., Preiser J.C. Microvascular blood flow is altered in patients with sepsis. Am. J. Respir. Crit. Care Med. 2002; 166: 98–104. DOI: 10.1164/rccm.200109–016OC
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