GlycoCheck: 117 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
Endothelial glycocalyx integrity in oncological patients
This study compared sublingual microvascular glycocalyx thickness (measured as perfused boundary region, PBR) in 64 cancer patients versus 32 controls with similar cardiovascular risk profiles. Cancer patients had significantly higher PBR values, indicating a thinner/damaged glycocalyx, even though arterial stiffness and standard echocardiographic measures were largely comparable. The impairment tracked with cancer stage rather than with traditional risk factors or anticancer treatment.
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Published paper
Mutations in the heparan sulfate backbone elongating enzymes EXT1 and EXT2 have no major effect on endothelial glycocalyx and the glomerular filtration barrier
Researchers tested whether people carrying a single defective copy of the heparan sulfate chain-elongating genes EXT1 or EXT2 (causing multiple osteochondromas) have a damaged endothelial glycocalyx or leaky glomerular filtration barrier. Using sublingual GlycoCheck measurements and urine albumin testing in 19 patients versus 19 matched controls, plus review of archived kidney biopsies from 24 osteochondroma cases, they found no meaningful differences. Only one archival case showed the rare fibrillar glomerular deposits previously described as 'glomerulopathy of hereditary multiple exostoses'.
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Published paper
Endothelial glycocalyx and microvascular perfusion are associated with carotid intima-media thickness and impaired myocardial deformation in psoriatic disease
This study compared sublingual endothelial glycocalyx and microvascular perfusion measures in 297 patients with psoriatic disease against 150 risk-factor-matched controls. Psoriatic patients showed a thinner glycocalyx (higher perfused boundary region) and poorer microvascular perfusion, and these changes tracked with disease severity, carotid intima-media thickness, coronary flow reserve, and left ventricular deformation.
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Published paper
Case Report: Endothelial Glycocalyx Damage in Critically ill Patients With SARS-CoV-2-Related Multisystem Inflammatory Syndrome (MIS-C)
This single-center case report describes two critically ill children with MIS-C in whom endothelial glycocalyx damage was documented using plasma syndecan-1 and sublingual video microscopy (GlycoCheck) alongside a marked systemic inflammatory response. Both children had abnormal perfused boundary region (PBR) values and reduced capillary density compared with a postoperative control child, and PBR normalized (1.68 and 1.54 microns) before transfer out of intensive care after immunoglobulin and methylprednisolone treatment plus supportive care. The authors argue that microcirculatory and glycocalyx involvement may partly explain shock, capillary leak, and prothrombotic features in MIS-C.
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Published paper
Association of Gestational Diabetes With Subclinical Cardiovascular Disease on Echocardiogram and Endothelial Function Testing (Abstract 12986)
This conference abstract reports a cross-sectional analysis of 217 women assessed roughly nine years after pregnancy, 53 of whom had a history of gestational diabetes. Women with prior gestational diabetes showed greater left ventricular wall thickness, worse diastolic function, and worse endothelial and glycocalyx measures (EndoPAT reactive hyperemia index and GlycoCheck parameters). Some hypertrophy differences were explained by BMI, hypertension, and diabetes, but the diastolic and vascular findings persisted after adjustment.
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Published paper
Impaired Endothelial Glycocalyx Predicts Adverse Outcome in Subjects Without Overt Cardiovascular Disease: a 6-Year Follow-up Study
In 600 subjects free of overt cardiovascular disease, researchers measured the perfused boundary region (PBR) in sublingual microvessels using sidestream dark-field imaging as an index of endothelial glycocalyx integrity, then followed them for 6 years. Higher PBR (indicating a thinner glycocalyx) independently predicted major adverse cardiovascular events beyond conventional risk factors and the European Heart SCORE.
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Published paper
Apremilast improves endothelial glycocalyx and microvascular perfusion: a possible protective mechanism against COVID-19
In this randomized comparison, 90 patients with psoriasis received apremilast, etanercept, or cyclosporine for 4 months, with sublingual glycocalyx (perfused boundary region, GlycoCheck/SDF imaging), arterial stiffness, and echocardiographic measures assessed before and after treatment. Only apremilast was associated with a reduction in PBR (indicating thicker glycocalyx) and it produced greater improvements in microvascular perfusion, pulse wave velocity, central systolic blood pressure, and left ventricular strain than the comparators. The authors speculate that glycocalyx protection could relate to reported benefits of apremilast in COVID-19, but no COVID-19 outcomes were studied.
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Published paper
Endothelial glycocalyx integrity and microvascular perfusion are associated with novel echocardiographic markers and carotid intima-media thickness in patients with psoriasis
Researchers used sublingual sidestream dark-field imaging (GlycoCheck) to compare endothelial glycocalyx barrier properties and microvascular perfusion in 297 psoriasis patients versus 150 risk-factor-adjusted controls. Psoriasis patients showed a thicker perfused boundary region (indicating a thinner glycocalyx) and poorer microvascular perfusion, which correlated with reduced coronary flow reserve, impaired left ventricular deformation, and greater carotid intima-media thickness.
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Published paper
Links between Endothelial Glycocalyx Changes and Microcirculatory Parameters in Septic Patients
In this single-center prospective observational study, sublingual microcirculation (Cytocam incident dark field imaging) and glycocalyx perfused boundary region (PBR, GlycoCheck) were compared between adults with sepsis or septic shock and healthy age-matched volunteers. Septic patients had significantly increased PBR (indicating thinner glycocalyx) across all vessel diameter classes, and PBR in the smallest capillaries correlated inversely with capillary density measures. The authors conclude there may be a functional link between glycocalyx damage in the smallest capillaries and sepsis-related microcirculatory alterations.
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Published paper
Microvascular Differences in Individuals With Obesity At Risk of Developing Cardiovascular Disease
In a cross-sectional analysis of 813 middle-aged adults with overweight/obesity, sublingual microcirculation was imaged using sidestream dark-field video microscopy with new GlycoCheck software that adds red blood cell velocity analysis. Participants at high 10-year cardiovascular risk (Framingham) had fewer perfused small capillaries and faster red cell velocity than low-risk participants, whereas velocity-corrected perfused boundary region (a glycocalyx index) did not differ between risk groups.
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Published paper
May We Use Non-Invasive Indices of Aortic Stiffness and Endothelial Glycocalyx as Biomarkers for Idiopathic Pulmonary Artery Hypertension Follow-Up?
This single-patient case report tracks three annual evaluations (2018-2020) of a woman with idiopathic pulmonary arterial hypertension, comparing invasive hemodynamics and exercise capacity with two non-invasive systemic vascular measures: carotid-femoral pulse wave velocity (aortic stiffness) and sublingual perfused boundary region (endothelial glycocalyx, GlycoCheck). When her pulmonary vascular resistance worsened, glycocalyx measures worsened (higher PBR, lower red blood cell filling), and both improved after treatment was changed. The authors suggest these indices deserve further study as non-invasive follow-up markers, but a single case cannot establish this.
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Published paper
Identification of novel sublingual parameters to analyze and diagnose microvascular dysfunction in sepsis: the NOSTRADAMUS study (link to Critical Care)
This single-center observational study used sublingual sidestream dark-field videomicroscopy with a new GlycoCheck software version to analyze microvessels in 1-micrometer diameter classes (4-25 um) in 34 septic ICU patients and 17 healthy controls. Sepsis was associated with loss of the very smallest capillaries, impaired capillary recruitment, and increased perfused boundary region (indicating a thinner/more permeable glycocalyx). The authors combined capillary blood volume and PBR into a composite 'Microvascular Health Score' that separated patients from controls and correlated with sepsis severity.
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Published paper
Non-invasive evaluation of macro- and microhemodynamic changes during induction of general anesthesia – A prospective observational single-blinded trial
In 150 women undergoing gynecologic surgery, non-invasive bioimpedance monitoring showed that induction of general anesthesia caused a larger fall in cardiac output (~40%) than in mean arterial pressure (~26%). Patients who later needed norepinephrine already had lower baseline cardiac output, stroke volume and contractility, and norepinephrine raised blood pressure without restoring cardiac performance. Sidestream dark-field imaging in a subset showed a 6.4% rise in perfused boundary region by the end of surgery, consistent with glycocalyx impairment.
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Published paper
Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study
In this randomized trial, 270 post-STEMI patients received either one cycle or two cycles of bilateral arm-cuff remote ischemic conditioning (RIC), or no conditioning. A single RIC cycle produced greater improvement in sublingual microvascular glycocalyx integrity (perfusion boundary region) and arterial stiffness, along with increases in cardioprotective microRNA-144 and nitrate-nitrite and reduced oxidative stress. At one year, single-cycle RIC was associated with greater reduction in left ventricular end-systolic volume, suggesting more favorable cardiac remodeling.
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Published paper
Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates
This prospective observational study used sidestream dark-field imaging with GlycoCheck software to measure the perfused boundary region (PBR, an inverse marker of endothelial glycocalyx thickness) in the skin microcirculation of 85 term and 39 preterm newborns. Preterm infants, especially those born before 30 weeks, had lower PBR (i.e., larger glycocalyx dimensions) than term infants, and PBR rose (glycocalyx thinned) with increasing postnatal age. Extremely preterm infants reached higher PBR values by 6-7 weeks of life than moderately preterm or term babies measured at the same corrected gestational age.
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Published paper
Does sublingual microscopy correlate with nailfold videocapillaroscopy in systemic sclerosis?
This single-center cross-sectional study compared automated sublingual videomicroscopy (GlycoCheck) with nailfold videocapillaroscopy (NVC), the standard test for scleroderma microvascular damage, in 39 systemic sclerosis patients on the same clinic day. Sublingual microvascular density correlated moderately with nailfold capillary number and inversely with the NVC microangiopathy evolution score. Functional measures (red blood cell fraction and glycocalyx perfused boundary region) did not correlate with NVC parameters in this mostly late-pattern cohort.
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Published paper
Assessment of the sublingual microcirculation with the GlycoCheck system: Reproducibility and examination conditions
This randomized, controlled methodological study tested how reproducible sublingual glycocalyx measurements with the GlycoCheck system (perfused boundary region, PBR, and red blood cell filling) are, and how they are affected by smoking, a high-calorie meal, and coffee. Reproducibility of single measurements was poor to moderate but improved substantially when 3-5 measurements were averaged, with no meaningful differences between investigators. All three acute exposures worsened PBR and RBC filling, with effects still detectable at 180 minutes.
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Published paper
Evaluation of jejunal microvasculature of healthy anesthetized dogs with sidestream dark field video microscopy
This veterinary study tested whether sidestream dark field (SDF) video microscopy could image and quantify the small blood vessels of the jejunum (small intestine) in 30 healthy anesthetized dogs during spay surgery. Imaging was feasible and produced reference values for microvascular density, red blood cell filling, vessel width, and the perfused boundary region (PBR), an indirect index of glycocalyx thickness. The authors conclude the technique warrants further study, including in dogs with intestinal disease.
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Published paper
Visual and Biochemical Evidence of Glycocalyx Disruption in Human Dengue Infection, and Association With Plasma Leakage Severity
This prospective observational study in Vietnam re-analyzed stored sublingual sidestream dark-field videos with GlycoCheck software and measured plasma syndecan-1 and endocan in 75 patients with confirmed dengue and 12 outpatients with other febrile illness. Patients with the most severe grade of plasma leakage showed a thinner, more degraded glycocalyx (higher perfused boundary region) and much higher plasma levels of shed glycocalyx proteoglycans during the critical illness phase. There were no significant glycocalyx differences between mild outpatient dengue and other febrile illnesses.
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Published paper
Microvascular dysfunction in COVID-19: the MYSTIC study
This prospective, multi-center cross-sectional study used sublingual sidestream dark-field video microscopy (GlycoCheck) plus blood biomarkers to characterize microvascular and endothelial glycocalyx changes in 23 hospitalized COVID-19 patients versus 15 healthy controls. Patients showed marked loss of small capillaries, slower red blood cell velocity, and evidence of glycocalyx damage, most pronounced in those on mechanical ventilation. Higher perfused boundary region (thinner glycocalyx) and lower ADAMTS13 were associated with 60-day in-hospital mortality.
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Published paper
Evaluation of endothelial glycocalyx in healthy volunteers – An observational study
This observational study measured the endothelial glycocalyx in 21 young healthy adults using sublingual sidestream dark-field imaging with GlycoCheck software (perfused boundary region, PBR) and plasma syndecan-1 by ELISA. It reports reference values for both measures in a healthy cohort, with a median PBR of 1.82 um and median syndecan-1 of 0.3 ng/ml. The authors note their values do not fully agree with previously published healthy-subject data.
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Published paper
Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19
Eighty patients with rheumatoid arthritis were randomized to 3 months of the IL-6 receptor blocker tocilizumab or to intensified conventional DMARDs plus glucocorticoids, with 40 age- and sex-matched healthy subjects as a comparison group. Endothelial glycocalyx thickness (sublingual perfused boundary region, PBR), arterial stiffness, echocardiographic myocardial work/strain, and inflammatory and oxidative stress markers were measured before and after treatment. Tocilizumab was associated with reduced PBR (indicating thicker glycocalyx), lower arterial stiffness, greater falls in CRP and oxidative stress markers, and greater improvement in myocardial deformation and work than conventional treatment.
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Published paper
Sex-related associations of high-density lipoprotein cholesterol with aortic stiffness and endothelial glycocalyx integrity in treated hypertensive patients
This cross-sectional study of 193 treated hypertensive patients examined whether HDL cholesterol levels relate to aortic stiffness (carotid-femoral pulse wave velocity) and endothelial glycocalyx integrity (sublingual perfused boundary region measured by sidestream dark-field imaging/GlycoCheck). Higher HDL-C was weakly and inversely associated with aortic stiffness in the whole group, and with PBR5-9 (a marker where higher values indicate a thinner glycocalyx) specifically in men, regardless of smoking status. No such glycocalyx association was seen in women, despite their higher HDL-C levels.
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Published paper
Immediate effects of whole blood donation on the endothelial surface layer and glycocalyx shedding
Researchers measured the sublingual microcirculation and blood markers of glycocalyx shedding in healthy volunteers immediately before and after donating 500 mL of whole blood. Using sidestream dark-field imaging with GlycoCheck software, they found no significant immediate change in the perfused boundary region (PBR) or red blood cell filling percentage. Plasma heparan sulfate and hyaluronan fell slightly while syndecan-1 was unchanged, suggesting the endothelial surface layer remains structurally stable after a standard donation.
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Published paper
Variability of Microcirculatory Measurements in Critically Ill Patients
This study tested how reproducible sublingual GlycoCheck microcirculation measurements are in 60 critically ill patients, using repeated measurements by one or two experienced observers. Single measurements of glycocalyx thickness (perfused boundary region) showed poor reliability, while red blood cell filling percentage and vessel density were more consistent. Averaging three consecutive measurements substantially improved reproducibility for all parameters.
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Published paper
Decreased endothelial glycocalyx thickness is an early predictor of mortality in sepsis
Researchers measured sublingual glycocalyx thickness (as the perfused boundary region, PBR) with sidestream dark-field imaging and GlycoCheck software within 24 hours of ICU admission in 21 septic patients, and compared results with plasma markers and survival. Patients who did not survive to hospital discharge had a thinner glycocalyx (higher PBR) than survivors, and admission PBR discriminated survivors from non-survivors moderately well. PBR correlated with angiopoietin-2 but not with syndecan-1 or severity scores.
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Published paper
Effects of Glucagon Like Peptide 1 Receptor Agonists, Sodium Glucose Cotransporter 2 Inhibitors, and Their Combination on Endothelial Glycocalyx, Arterial Function, and Myocardial Work Index in Patients With Type 2 Diabetes Mellitus After 12 Month Treatme
In this 12-month randomized trial, 160 patients with type 2 diabetes were assigned to add-on insulin, liraglutide (GLP-1RA), empagliflozin (SGLT-2i), or the GLP-1RA/SGLT-2i combination. Despite similar HbA1c reductions across groups, the newer agents and especially the combination produced greater improvements in sublingual glycocalyx thickness (perfused boundary region), arterial stiffness, central blood pressure, and echocardiographic myocardial strain and work indices than insulin.
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Published paper
Microvascular Alterations During Cardiac Surgery Using a Heparin or Phosphorylcholine-Coated Circuit
In this single-center randomized, blinded trial, 26 adults having on-pump CABG surgery received either a heparin-coated or a phosphorylcholine-coated cardiopulmonary bypass circuit. Sublingual sidestream dark-field imaging (GlycoCheck) and plasma shedding markers showed glycocalyx thinning and shedding in the phosphorylcholine group but not the heparin-coated group, while the fall in perfused vessel density during bypass was similar in both groups.
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Published paper
Uncoupling of Microvascular Blood Flow and Capillary Density in Vascular Cognitive Impairment
Researchers used sublingual video microscopy (GlycoCheck system) to compare how the smallest blood vessels respond to spontaneous changes in blood flow in 15 men with vascular cognitive impairment from cerebral small vessel disease and 15 male controls. In healthy controls, the number of red-cell-perfused capillaries rose as feed vessel flow rose, whereas in patients with cognitive impairment it did not. The authors interpret this as an uncoupling of microvascular flow from perfused capillary density, which could limit oxygen and nutrient exchange when metabolic demand increases.
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Published paper
Tie2 Activation Promotes Protection and Reconstitution of the Endothelial Glycocalyx in Human Sepsis
Researchers measured the perfused boundary region (PBR), an inverse marker of endothelial glycocalyx thickness, in sublingual microvessels of septic patients and nonseptic controls, and found thicker PBR (thinner glycocalyx) in sepsis that correlated with serum angiopoietin-2 levels. Serum from septic patients thinned the glycocalyx of cultured human endothelial cells, an effect abolished by blocking angiopoietin-2 or activating the Tie2 receptor. Mechanistically, damage required heparan sulfate loss via heparanase, which Tie2 activation suppressed; Tie2 activation after injury also accelerated glycocalyx recovery.
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Published paper
Association of sublingual microcirculation parameters and endothelial glycocalyx dimensions in resuscitated sepsis
In 30 ICU patients with resuscitated sepsis and 10 healthy controls, researchers simultaneously measured endothelial glycocalyx dimensions (sublingual perfused boundary region, PBR, via GlycoCheck) and conventional sublingual microcirculation parameters (incident dark field imaging). Septic patients had both thicker PBR (indicating glycocalyx damage) and impaired microvascular perfusion, and both correlated with markers of illness severity, but the two sets of measures did not correlate with each other. PBR values agreed well with circulating syndecan-1 and with glycocalyx thickness measured by atomic force microscopy in endothelial cells exposed to patient serum.
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Published paper
Impaired Arterial Elastic Properties and Endothelial Glycocalyx in Patients with Embolic Stroke of Undetermined Source
This case-control study compared 90 patients who had an embolic stroke of undetermined source with 90 controls carrying similar cardiovascular risk factors. ESUS patients had thinner endothelial glycocalyx (higher sublingual perfused boundary region), stiffer arteries (higher pulse wave velocity), more oxidative stress, and impaired left atrial function. Glycocalyx damage correlated with arterial stiffness, which in turn related to left atrial reservoir strain.
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Published paper
Effects of Different Antidiabetic Medications on Endothelial Glycocalyx, Myocardial Function, and Vascular Function in Type 2 Diabetic Patients: One Year Follow-Up Study
One hundred people with poorly controlled type 2 diabetes were assessed before and 12 months after intensifying their antidiabetic treatment, with measurements of arterial stiffness, brachial artery flow-mediated dilation, sublingual endothelial glycocalyx (perfused boundary region by GlycoCheck), heart muscle deformation on echocardiography, and blood markers of oxidative stress. Average HbA1c fell from 8.9% to 7.1%, and this was accompanied by lower arterial stiffness, a smaller perfused boundary region (suggesting a thicker/less penetrable glycocalyx), better endothelial and left ventricular function, and lower oxidative stress markers. In multivariable analysis, incretin-based drugs (GLP-1 receptor agonists and DPP-4 inhibitors) were associated with these improvements over and above the fall in HbA1c.
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Published paper
Effects of high-intensity interval training on microvascular glycocalyx and associated microRNAs
Fifty healthy young adults completed a 4-week high-intensity interval training (HIIT) program consisting of 4 x 30-s all-out runs, with sublingual microvascular imaging (sidestream dark-field, perfused boundary region) before and after. Exercise capacity correlated with glycocalyx measures, and several circulating microRNAs were upregulated by HIIT, with baseline miR-143 predicting later glycocalyx changes. The authors conclude HIIT alters the endothelial glycocalyx of the microvasculature and that miRNAs may serve as markers of early vascular adaptation.
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Published paper
Sublingual endothelial glycocalyx and atherosclerosis. A cross-sectional study
In the largest study of its kind, sublingual perfused boundary region (PBR, an indirect index of endothelial glycocalyx thickness) was measured once in 6,169 multi-ethnic adults and related to classical cardiovascular risk factors and self-reported cardiovascular disease. The smallest glycocalyx size (highest PBR quartile) was independently associated with female sex, older age, and diabetes, but not with prevalent cardiovascular disease, coronary heart disease/revascularization, or stroke. The authors conclude that PBR-estimated glycocalyx size does not track a high cardiovascular risk profile in a general population.
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Published paper
Early Onset Preeclampsia Is Associated With Glycocalyx Degradation and Reduced Microvascular Perfusion
This exploratory cross-sectional study used sublingual sidestream dark field imaging (GlycoCheck) plus blood markers to compare endothelial glycocalyx status in 137 third-trimester pregnant women. Women with early-onset preeclampsia (<34 weeks) showed greater glycocalyx degradation (higher perfused boundary region) and fewer capillaries filled with red blood cells than normotensive women, women with gestational diabetes, or those with late-onset preeclampsia. Circulating heparan sulfate proteoglycans and hyaluronic acid were also elevated in early-onset preeclampsia.
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Published paper
Increase in perfused boundary region of endothelial glycocalyx is associated with higher prevalence of ischemic heart disease and lesions of microcirculation and vascular wall.
This cross-sectional study measured the perfused boundary region (PBR), an index of red blood cell penetration into the endothelial glycocalyx, using sidestream dark-field capillaroscopy in 208 middle-aged patients. Higher PBR values (above about 2 micrometers) were associated with a greater prevalence of ischemic heart disease and cerebral atherosclerosis, as well as structural and functional abnormalities of the arterial wall and skin microcirculation. The authors propose PBR as a reproducible, non-invasive candidate marker of cardiovascular disease.
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Published paper
Derangement of the endothelial glycocalyx in sepsis
This narrative review describes the structure and functions of the endothelial glycocalyx and how it is degraded during sepsis. It covers glycocalyx roles in leukocyte adhesion, anticoagulation, vascular permeability and mechanosensing, methods of assessment (circulating syndecan-1, heparan sulfate, hyaluronan; electron and intravital microscopy; sidestream dark-field imaging with automated PBR analysis), and candidate protective strategies. The authors conclude that no treatment has yet been proven clinically effective and that links between glycocalyx damage, sepsis severity and DIC remain inadequately defined.
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Published paper
Induced Trf2 deletion leads to aging vascular phenotype in mice associated with arterial telomere uncapping, senescence signaling, and oxidative stress
Researchers deleted the telomere-protecting protein Trf2 in adult mice to force telomere 'uncapping' without shortening telomeres, then measured artery and microvessel function. Trf2 deletion produced senescence signaling, oxidative stress, impaired nitric-oxide-dependent vasodilation, thinner endothelial glycocalyx, reduced microvascular perfusion, and modestly higher systolic blood pressure — a pattern resembling normal vascular aging.
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Published paper
Neuraxial anesthesia is less harmful to the endothelial glycocalyx during elective joint surgery compared to general anesthesia1,2.
This prospective observational study used sidestream dark-field imaging of the sublingual microcirculation to measure the perfused boundary region (PBR), an inverse marker of endothelial glycocalyx thickness, before and 2 hours after elective hip or knee replacement. PBR increased significantly after surgery in both anesthesia groups, indicating glycocalyx perturbation. The increase was greater in patients receiving general anesthesia than in those receiving neuraxial anesthesia.
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