The role of endothelial glycocalyx in health and disease

Yilmaz, Onur; Afsar, Barış; Ortíz, Alberto; Kanbay, Mehmet

doi:10.1093/ckj/sfz042

Cited by 77 publications

(56 citation statements)

References 101 publications

(126 reference statements)

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“…The endothelial glycocalyx layer has an essential role in maintaining the normal fluid homeostasis of the body ( 32 ), but is fragile and can be damaged by a number of pathophysiological conditions and interventions.…”

Section: Endothelial Glycocalyx Layer (Egl)mentioning

confidence: 99%

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock

Johnson

Fatemi

Winlow

2020

Front. Cardiovasc. Med.

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The emergence of the COVID-19 virus and the subsequent pandemic have driven a great deal of research activity. The effects of COVID-19 are caused by the severe respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is the underlying actions of SARs-CoV-2 virions on the endothelial glycocalyx that we consider here. One of the key factors in COVID-19 infection is its almost unique age-related profile, with a doubling in mortality every 10 years after the age of 50. The endothelial glycocalyx layer is essential in maintaining normal fluid homeostasis, but is fragile and prone to pathophysiological damage. It is physiologically significant in capillary microcirculation and in fluid distribution to the tissues. Human serum albumin (HSA), the most abundant protein in plasma, is created in the liver which also maintains its concentration, but this reduces by 10-15% after 50 years of age. HSA transports hormones, free fatty acids and maintains oncotic pressure, but SARS-CoV-2 virions bind competitively to HSA diminishing its normal transport function. Furthermore, hypoalbuminemia is frequently observed in patients with such conditions as diabetes, hypertension, and chronic heart failure, i.e., those most vulnerable to SARS-CoV-2 infection. Hypoalbuminemia, coagulopathy, and vascular disease have been linked in COVID-19 and have been shown to predict outcome independent of age and morbidity. Hypoalbuminemia is also known factor in sepsis and Acute respiratory distress syndrome (ARDS) occurs when fluids build-up in the alveoli and it is associated with sepsis, whose mechanism is systemic, being associated with the fluid and logistic mechanisms of the circulation. Glycocalyx damage is associated with changes plasma protein concentration, particularly HSA and blockage of albumin transport can produce the systemic symptoms seen in SARS-CoV-2 infection and sepsis. We therefore conclude that albumin binding to SARS-CoV-2 virions may inhibit the formation of the endothelial glycocalyx by inhibition of albumin transport binding sites. We postulate that albumin therapy to replace bound albumin might alleviate some of the symptoms leading to sepsis and that clinical trials to test this postulation should be initiated as a matter of urgency.

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Section: Endothelial Glycocalyx Layer (Egl)mentioning

confidence: 99%

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock

Johnson

Fatemi

Winlow

2020

Front. Cardiovasc. Med.

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“…It prevents the direct contact of circulating blood cells with endothelial surface ( Lekakis et al, 2011 ). Pathophysiological conditions, such as inflammation and oxidative stress, are associated with glycocalyx impairment ( Yilmaz et al, 2019 ). In particularly, reactive oxygen species (ROS) induce an acute but rapidly reversible impairment of glycocalyx structure after antioxidant treatment ( Singh et al, 2013 ).…”

Section: Introductionmentioning

confidence: 99%

Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

Ikonomidis

Pavlidis

Katsimbri

et al. 2020

Food and Chemical Toxicology

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We investigated the effects of tocilizumab on endothelial glycocalyx, a determinant of vascular permeability, and myocardial function in rheumatoid arthritis (RA). Eighty RA patients were randomized to tocilizumab (n = 40) or conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) and glucocorticoids (GC) (n = 40) for 3 months. Forty healthy subjects with similar age and sex served as controls. We measured: (a)perfused boundary region (PBR) of the sublingual arterial microvessels (increased PBR indicates reduced glycocalyx thickness), (b)pulse wave velocity (PWV), (c)global LV longitudinal strain (GLS), (d)global work index (GWI) using speckle tracking echocardiography and e)C-reactive protein (CRP), malondialdehyde (MDA) and protein carbonyls (PCs) as oxidative stress markers at baseline and post-treatment. Compared to controls, RA patients had impaired glycocalyx and myocardial deformation markers (P < 0.05). Compared with baseline, tocilizumab reduced PBR(2.14 ± 0.2 versus 1.97 ± 0.2 μm; P < 0.05) while no significant differences were observed post-csDMARDs + GC(P > 0.05). Compared with csDMARDs + GC, tocilizumab achieved a greater increase of GLS, GWI and reduction of MDA, PCs and CRP(P < 0.05). The percent improvement of glycocalyx thickness (PBR) was associated with the percent decrease of PWV, MDA, PCs and the percent improvement of GLS and GWI(P < 0.05). Tocilizumab improves endothelial function leading to a greater increase of effective myocardial work than csDMARDs + GC through a profound reduction of inflammatory burden and oxidative stress. This mechanism may explain the effects of tocilizumab on COVID-19. Clinical trial registration url: https://www.clinicaltrials.gov . Unique identifier: NCT03288584.

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“…The EG is a complex, highly versatile structure that has essential roles in vascular integrity and function, and destruction of the EG has been described in the pathogenesis of micro- and macrovascular diseases 27 . Prematurity and low birth weight are known risk factors for cardiovascular disease, however, the exact mechanisms underlying this increased risk profile are still insufficiently understood, and the contribution of the EG remains elusive 1 .…”

Section: Discussionmentioning

confidence: 99%

Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates

Puchwein-Schwepcke¹,

Artmann²,

Rajwich³

et al. 2021

Sci Rep

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Prematurity predisposes to cardiovascular disease; however the underlying mechanisms remain elusive. Disturbance of the endothelial glycocalyx (EG), an important regulator of vessel function, is thought to contribute to vascular pathology. Here, we studied the EG with respect to gestational and postnatal age in preterm and term neonates. The Perfused Boundary Region (PBR), an inverse measure of glycocalyx thickness, was measured postnatally in 85 term and 39 preterm neonates. Preterm neonates were further analyzed in two subgroups i.e., neonates born < 30 weeks gestational age (group A) and neonates born ≥ 30 weeks (group B). In preterm neonates, weekly follow-up measurements were performed if possible. PBR differed significantly between preterm and term neonates with lowest values representing largest EG dimension in extremely premature infants possibly reflecting its importance in fetal vascular development. Linear regression revealed a dependence of PBR on both, gestational age and postnatal age. Furthermore, hematocrit predicted longitudinal PBR changes. PBR measured in group A at a corrected age of > 30 weeks was significantly higher than in group B at birth, pointing towards an alteration of intrinsic maturational effects by extrinsic factors. These changes might contribute to the increased cardiovascular risk associated with extreme prematurity.

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The role of endothelial glycocalyx in health and disease

Cited by 77 publications

References 101 publications

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock

SARS-CoV-2 Bound Human Serum Albumin and Systemic Septic Shock

Tocilizumab improves oxidative stress and endothelial glycocalyx: A mechanism that may explain the effects of biological treatment on COVID-19

Effect of gestational age and postnatal age on the endothelial glycocalyx in neonates

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