Scientific Literature on the Endothelial Glycocalyx

A Research Overview

March 8, 2022

On this page we introduce some of the important scientific studies that have been conducted into the endothelial glycocalyx (EGX). This is not an exhaustive inventory, but a sample of the many research avenues currently being pursued in relation to this critical physiological structure.

Since vascular health affects every organ and system in the body, the endothelial glycocalyx is essential to human health.

About the Endothelial Glycocalyx

The endothelial glycocalyx (EGX) is the inner lining of every blood vessel in the human body. Composed of glycoproteins, proteoglycans, glycosaminoglycans, and glycolipids, the endothelial glycocalyx is a selectively permeable barrier. It mediates biochemical and biomechanical signals in the circulating blood for optimal endothelial function.

From a clinical perspective, these are a few of the most relevant functions that the EGX performs:

  • Protects the endothelium from harmful particles
  • Houses extracellular superoxide dismutase (an important antioxidant)
  • Triggers shear-induced nitric oxide (NO) production
  • Buffers blood sodium

A Brief Summary of the EGX’s Structure

The carbohydrate-rich structure of the EGX includes ‘backbone” molecules that tether the matrix to the endothelium. The backbone molecules are primarily proteoglycans with various kinds of glycosaminoglycan chains, including heparan sulfate, as well as glycoproteins.

Embedded in the mesh that is bound to the endothelium are found many soluble components derived from both the plasma and the endothelium.

The entire EGX structure is highly dynamic. It is susceptible to shedding through shear stress and enzymatic action, and a healthy EGX exhibits a dynamic equilibrium between degradation and synthesis. The structure’s thickness and exact composition vary in response to both blood flow and the contents of the plasma. There is also a dynamic balance between the components attached to the endothelial wall and those that are free-floating nearer the lumen.

The EGX comprises a significant percentage of the total volume of the microvasculature and plays a decisive role in its functionality.

An Explosion of Studies

The scientific significance of the EGX was gradually recognized. With this came an increase in scientific studies, which has grown exponentially in the last two decades.

Important Areas of Focus

In the growing scientific literature on the EGX, there are several areas of research that hold significant potential. Some of these are listed below, with a brief explanation of their importance.

Cardiovascular health:
The EGX plays an essential role in cardiovascular health because it mediates the passage of lipids and other blood contents through the arterial wall.

Vasodilation
The EGX triggers the production of nitric oxide (NO) in the endothelium. NO is an important vessel dilator and plays a central role in the maintenance of normal blood pressure.

Brain health:
In the field of brain health and cognitive function, increasing attention has been given to the vascular dimension.  Numerous studies have shown the important role of the EGX in the flow of blood through the cerebral microvasculature.

Kidney function:
The microvasculature plays a decisive role in kidney health, because renal function depends on adequate density of perfused capillaries. Maintaining normal endothelial function within the microvasculature is essential to the kidneys, and this is only possible with a healthy EGX.

Microvascular function at the extremities:
It is well understood that normal microvascular function throughout the body depends on healthy blood flow, and this in turn requires sufficient production of NO to maintain dilation of the small blood vessels. Studies have shown the essential role of the EGX in sustaining normal microvascular function.

 

Scientific research into the EGX continues to expand, with attention being given to additional structures and functions.

This is a sample of major studies conducted into the EGX. For convenience, we’ve grouped them under headings, though the content of the studies often overlaps different fields.

 

General EGX Citations

Alphonsus CS, Rodseth RN. The endothelial glycocalyx: a review of the vascular barrier. Anaesthesia. 2014;69(7):777-784. doi:10.1111/anae.12661

Bermejo-Martin JF, Martín-Fernandez M, López-Mestanza C, Duque P, Almansa R. Shared Features of Endothelial Dysfunction between Sepsis and Its Preceding Risk Factors (Aging and Chronic Disease). J Clin Med. 2018;7(11). doi:10.3390/jcm7110400

Cao R-N, Tang L, Xia Z-Y, Xia R. Endothelial glycocalyx as a potential therapeutic  target in organ injuries. Chinese Medical Journal. 2019;132(8):963-975. doi:10.1097/CM9.0000000000000177

Cabrales P, Vázquez BYS, Tsai AG, Intaglietta M. Microvascular and capillary perfusion following glycocalyx degradation. J Appl Physiol (1985). 2007;102(6):2251-2259. doi:10.1152/japplphysiol.01155.2006

Delgadillo LF, Marsh GA, Waugh RE. Endothelial Glycocalyx Layer Properties and Its Ability to Limit Leukocyte Adhesion. Biophys J. 2020;118(7):1564-1575. doi:10.1016/j.bpj.2020.02.010

Jedlicka J, Becker BF, Chappell D. Endothelial Glycocalyx. Crit Care Clin. 2020;36(2):217-232. doi:10.1016/j.ccc.2019.12.007

Joffre J, Hellman J, Ince C, Ait-Oufella H. Endothelial Responses in Sepsis. Am J Respir Crit Care Med. 2020;202(3):361-370. doi:10.1164/rccm.201910-1911TR

Kolářová H, Ambrůzová B, Švihálková Šindlerová L, Klinke A, Kubala L. Modulation of Endothelial Glycocalyx Structure under Inflammatory Conditions. Mediators Inflamm. 2014;2014. doi:10.1155/2014/694312

McClatchey PM, Schafer M, Hunter KS, Reusch JEB. The endothelial glycocalyx promotes homogenous blood flow distribution within the microvasculature. Am J Physiol Heart Circ Physiol. 2016;311(1):H168-H176. doi:10.1152/ajpheart.00132.2016

Rovas A, Lukasz A-H, Vink H, et al. Bedside analysis of the sublingual microvascular glycocalyx in the emergency room and intensive care unit – the GlycoNurse study. Scand J Trauma Resusc Emerg Med. 2018;26. doi:10.1186/s13049-018-0483-4

Schött U, Solomon C, Fries D, Bentzer P. The endothelial glycocalyx and its disruption, protection and regeneration: a narrative review. Scand J Trauma Resusc Emerg Med. 2016;24. doi:10.1186/s13049-016-0239-y

Ushiyama A, Kataoka H, Iijima T. Glycocalyx and its involvement in clinical pathophysiologies. J Intensive Care. 2016;4(1). doi:10.1186/s40560-016-0182-z

VanTeeffelen JW, Brands J, Stroes ES, Vink H. Endothelial Glycocalyx: Sweet Shield of Blood Vessels. Trends in Cardiovascular Medicine. 2007;17(3):101-105. doi:10.1016/j.tcm.2007.02.002

Weinbaum S, Cancel LM, Fu BM, Tarbell JM. The Glycocalyx and Its Role in Vascular Physiology and Vascular Related Diseases. Cardiovasc Eng Technol. Published online September 21, 2020:1-35. doi:10.1007/s13239-020-00485-9

Weissgerber TL, Garcia-Valencia O, Milic NM, et al. Early Onset Preeclampsia Is Associated With Glycocalyx Degradation and Reduced Microvascular Perfusion. J Am Heart Assoc. 2019;8(4):e010647. doi:10.1161/JAHA.118.010647

Blood vessel walls

Akhtar S, Sharma A. Endothelial dysfunction sustains immune response in atherosclerosis: potential cause for ineffectiveness of prevailing drugs. International Reviews of Immunology. 2021;0(0):1-19. doi:10.1080/08830185.2020.1866568

Brands J, Hubel CA, Althouse A, Reis SE, Pacella JJ. Noninvasive sublingual microvascular imaging reveals sex-specific reduction in glycocalyx barrier properties in patients with coronary artery disease. Physiol Rep. 2020;8(2):e14351. doi:10.14814/phy2.14351

Cancel LM, Ebong EE, Mensah S, Hirshberg C, Tarbell JM. Endothelial glycocalyx, apoptosis and inflammation in an atherosclerotic mouse model. Atherosclerosis. 2016;252:136-146. doi:10.1016/j.atherosclerosis.2016.07.930

Eckardt V, Weber C, Hundelshausen P von. Glycans and Glycan-Binding Proteins in Atherosclerosis. Thromb Haemost. 2019;119(8):1265-1273. doi:10.1055/s-0039-1692720

Harding IC, Mitra R, Mensah SA, Nersesyan A, Bal NN, Ebong EE. Endothelial barrier reinforcement relies on flow-regulated glycocalyx, a potential therapeutic target. Biorheology. 2019;56(2-3):131-149. doi:10.3233/BIR-180205

Liu X, Fan Y, Deng X. Effect of the endothelial glycocalyx layer on arterial LDL transport under normal and high pressure. Journal of Theoretical Biology. 2011;283(1):71-81. doi:10.1016/j.jtbi.2011.05.030

Mensah SA, Nersesyan AA, Ebong EE. Endothelial Glycocalyx-Mediated Intercellular Interactions: Mechanisms and Implications for Atherosclerosis and Cancer Metastasis. Cardiovasc Eng Technol. Published online September 30, 2020. doi:10.1007/s13239-020-00487-7

Mitra R, O’Neil GL, Harding IC, Cheng MJ, Mensah SA, Ebong EE. Glycocalyx in Atherosclerosis-Relevant Endothelium Function and as a Therapeutic Target. Curr Atheroscler Rep. 2017;19(12). doi:10.1007/s11883-017-0691-9

Nemoto T, Minami Y, Yamaoka-Tojo M, et al. Endothelial glycocalyx and severity and vulnerability of coronary plaque in patients with coronary artery disease. Atherosclerosis. 2020;302:1-7. doi:10.1016/j.atherosclerosis.2020.04.014

Noble MIM, Drake-Holland AJ, Vink H. Hypothesis: arterial glycocalyx dysfunction is the first step in the atherothrombotic process. QJM: An International Journal of Medicine. 2008;101(7):513-518. doi:10.1093/qjmed/hcn024

Nieuwdorp M, Meuwese MC, Vink H, Hoekstra JB, Kastelein JJ, Stroes ES. The endothelial glycocalyx: a potential barrier between health and vascular disease. Current Opinion in Lipidology. 2005;16(5):507-511. doi:10.1097/01.mol.0000181325.08926.9c

Vascular Health

Facchini L, Bellin A, Toro EF. Modeling Loss of Microvascular Wall Homeostasis during Glycocalyx Deterioration and Hypertension that Impacts Plasma Filtration and Solute Exchange. Curr Neurovasc Res. 2016;13(2):147-155. doi:10.2174/1567202613666160223121415

Ikonomidis I, Voumvourakis A, Makavos G, et al. Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives. J Clin Hypertens (Greenwich). 2018;20(4):672-679. doi:10.1111/jch.13236

Brain health

Ando Y, Okada H, Takemura G, et al. Brain-Specific Ultrastructure of Capillary Endothelial Glycocalyx and Its Possible Contribution for Blood Brain Barrier. Sci Rep. 2018;8(1):17523. doi:10.1038/s41598-018-35976-2

Haeren RHL, Rijkers K, Schijns OEMG, et al. In vivo assessment of the human cerebral microcirculation and its glycocalyx: A technical report. J Neurosci Methods. 2018;303:114-125. doi:10.1016/j.jneumeth.2018.03.009

Nian K, Harding IC, Herman IM, Ebong EE. Blood-Brain Barrier Damage in Ischemic Stroke and Its Regulation by Endothelial Mechanotransduction. Front Physiol. 2020;11:605398. doi:10.3389/fphys.2020.605398

Zhao F, Zhong L, Luo Y. Endothelial glycocalyx as an important factor in composition of blood-brain barrier. CNS Neurosci Ther. 2021;27(1):26-35. doi:10.1111/cns.13560

Kidney function

Butler MJ, Down CJ, Foster RR, Satchell SC. The Pathological Relevance of Increased Endothelial Glycocalyx Permeability. Am J Pathol. 2020;190(4):742-751. doi:10.1016/j.ajpath.2019.11.015

Jacob M, Chappell D, Becker BF. Regulation of blood flow and volume exchange across the microcirculation. Crit Care. 2016;20. doi:10.1186/s13054-016-1485-0

Liew H, Roberts MA, MacGinley R, McMahon LP. Endothelial glycocalyx in health and kidney disease: Rising star or false Dawn? Nephrology. 2017;22(12):940-946. doi:10.1111/nep.13161

McClatchey PM, Schafer M, Hunter KS, Reusch JEB. The endothelial glycocalyx promotes homogenous blood flow distribution within the microvasculature. Am J Physiol Heart Circ Physiol. 2016;311(1):H168-H176. doi:10.1152/ajpheart.00132.2016

Nieuwdorp M, Mooij HL, Kroon J, et al. Endothelial Glycocalyx Damage Coincides With Microalbuminuria in Type 1 Diabetes. Diabetes. 2006;55(4):1127-1132. doi:10.2337/diabetes.55.04.06.db05-1619

Salmon AHJ, Satchell SC. Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability. J Pathol. 2012;226(4):562-574. doi:10.1002/path.3964

Snoeijs MG, Vink H, Voesten N, et al. Acute ischemic injury to the renal microvasculature in human kidney transplantation. Am J Physiol Renal Physiol. 2010;299(5):F1134-1140. doi:10.1152/ajprenal.00158.2010

Yilmaz O, Afsar B, Ortiz A, Kanbay M. The role of endothelial glycocalyx in health and disease. Clin Kidney J. 2019;12(5):611-619. doi:10.1093/ckj/sfz042

Microvasculature

Cabrales P, Vázquez BYS, Tsai AG, Intaglietta M. Microvascular and capillary perfusion following glycocalyx degradation. J Appl Physiol (1985). 2007;102(6):2251-2259. doi:10.1152/japplphysiol.01155.2006

McClatchey PM, Schafer M, Hunter KS, Reusch JEB. The endothelial glycocalyx promotes homogenous blood flow distribution within the microvasculature. Am J Physiol Heart Circ Physiol. 2016;311(1):H168-H176. doi:10.1152/ajpheart.00132.2016

Ikonomidis I, Voumvourakis A, Makavos G, et al. Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives. J Clin Hypertens (Greenwich). 2018;20(4):672-679. doi:10.1111/jch.13236

Østergaard L. Blood flow, capillary transit times, and tissue oxygenation. The centennial of capillary recruitment. J Appl Physiol (1985). Published online October 8, 2020. doi:10.1152/japplphysiol.00537.2020

Important Notice

The information on this webpage is for licensed healthcare practitioner education only, and is not to be disseminated to the general public.