Protease activity and the role of the endothelial glycocalyx in inflammation

Lipowsky, Herbert H.

doi:10.1016/j.ddmod.2011.05.004

Cited by 57 publications

(45 citation statements)

References 75 publications

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“…Endothelial glycocalyx in hypertensive rats was significantly impaired compared to controls . At the sites where glycocalyx was degraded, there was a remarkable adhesion of leucocytes and platelets on the luminal surface of endothelial cells …”

Section: Discussionmentioning

confidence: 99%

Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives

Ikonomidis

Voumvourakis

Makavos

et al. 2018

J of Clinical Hypertension

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We investigated the association of endothelial glycocalyx damage with arterial stiffness, impairment of coronary microcirculatory function, and LV myocardial deformation in 320 untreated hypertensives and 160 controls. We measured perfused boundary region (PBR) of the sublingual microvessels, a marker inversely related with glycocalyx thickness, coronary flow reserve (CFR), and Global Longitudinal strain (GLS) by echocardiography, pulse wave velocity (PWV), and central systolic blood pressure (cSBP). Hypertensives had higher PBR, PWV cSBP, and lower CFR and GLS than controls (P < .05). In hypertensives, increased PBR was associated with increased cSBP, PWV, and decreased CFR and GLS after adjustment for age, sex, BMI, smoking LV mass, heart rate, hyperlipidemia, and office SBP (P < .05). PBR had an additive value to PWV, CFR, and office SBP for the prediction of abnormal GLS (x 2 = 2.4-3.8, P for change = .03). Endothelial glycocalyx is impaired in untreated hypertensives and is related to arterial stiffness, coronary, and myocardial dysfunction. | 673IKONOMIDIS et al.reserve (CFR), a marker of coronary microcirculatory function, is related to arterial stiffness and is impaired in hypertensive heart disease. 22 The effect of endothelial glycocalyx damage on arterial wall properties, coronary flow reserve, and LV myocardial deformation has not been clarified.We hypothesized that endothelial glycocalyx is impaired in newly diagnosed untreated hypertensives, leading to impaired arterial elasticity, coronary flow reserve, and consequently, abnormal myocardial deformation. Therefore, we investigated the association of endothelial glycocalyx damage with pulse wave velocity, coronary flow reserve, and LV myocardial deformation in untreated hypertensives. | MATERIAL S AND ME THODS | Study populationOut of 348 consecutive patients with new onset essential hypertension who attended our outpatient hypertension clinic, 320 patients (mean age: 51 ± 11 years, 67% males) with normal ejection fraction (>60%) had adequate 2-dimensional echocardiography images for the analysis of speckle parameters (feasibility of the method 92%). The diagnosis of essential hypertension was defined as One-hundred and sixty normotensive individuals (age:48 ± 13 years, 66% males) who visited our outpatient clinic for a routine check-up were selected using a ratio of 1 control to 2 hypertensive patients as controls.Exclusion criteria were history of diabetes, familiar hyperlipidemia, coronary artery disease (CAD), cardiomyopathy, and chronic pulmonary disease. All patients and controls had no history of CAD, normal resting electrocardiogram, and underwent a non-invasive test (thallium scintigraphy after a treadmill exercise test or dobutamine stress echocardiography) to exclude myocardial ischemia. None of the female patients were on hormone replacement treatment. None of the patients or controls were on any kind of medication, including statins. All patients and controls had a glomerular filtration rate (GFR) > 60 mL/min/1.732 (MDRD formula) at enr...

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Section: Discussionmentioning

confidence: 99%

Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives

Ikonomidis

Voumvourakis

Makavos

et al. 2018

J of Clinical Hypertension

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“…In cultured endothelial cells, high shear stress increases production of the gene KLF2,40 whose downstream effects include increased production of proteoglycan 1, secretory granule (PRG1) and various sulfotransferases (SULF1, SULF2)29 that are present in the Golgi to modify nascent HS. Development of a thicker glycocalyx may serve the atheroprotective phenotype by providing steric hindrances to infiltrating cytokines and macrophages (reviewed in Lipowsky23). …”

Section: Discussionmentioning

confidence: 99%

Heparan Sulfate Regrowth Profiles Under Laminar Shear Flow Following Enzymatic Degradation

et al. 2013

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Abstract-The local hemodynamic shear stress waveforms present in an artery dictate the endothelial cell phenotype. The observed decrease of the apical glycocalyx layer on the endothelium in atheroprone regions of the circulation suggests that the glycocalyx may have a central role in determining atherosclerotic plaque formation. However, the kinetics for the cells' ability to adapt its glycocalyx to the environment have not been quantitatively resolved. Here we report that the heparan sulfate component of the glycocalyx of HUVECs increases by 1.4-fold following the onset of high shear stress, compared to static cultured cells, with a time constant of 19 h. Cell morphology experiments show that 12 h are required for the cells to elongate, but only after 36 h have the cells reached maximal alignment to the flow vector. Our findings demonstrate that following enzymatic degradation, heparan sulfate is restored to the cell surface within 12 h under flow whereas the time required is 20 h under static conditions. We also propose a model describing the contribution of endocytosis and exocytosis to apical heparan sulfate expression. The change in HS regrowth kinetics from static to high-shear EC phenotype implies a differential in the rate of endocytic and exocytic membrane turnover.

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“…Indeed, a damaged and/or reduced glycocalyx has been linked to various vascular pathologies 2, 3, 5, 7, 10, 14, 23, 24 . However, studies exploring the role and structure of the glycocalyx have yet to directly quantify the anti-thrombogenic properties of this important endothelial coating.…”

Section: Discussionmentioning

confidence: 99%

New Functional Tools for Antithrombogenic Activity Assessment of Live Surface Glycocalyx

Dimitrievska

Gui

Weyers

et al. 2016

ATVB

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Objective It is widely accepted that the presence of a glycosaminoglycan-rich glycocalyx is essential for endothelialized vasculature health; in fact, a damaged or impaired glycocalyx has been demonstrated in a number of vascular diseases. Currently, there are no methods that characterize glycocalyx functionality, thus limiting investigators’ ability to assess the role of the glycocalyx in vascular health. Approach and Results We have developed novel easy to use in vitro assays that directly quantify live endothelialized surface’s functional heparin weights and their anti-coagulant capacity to inactivate Factor Xa and thrombin. Using our assays, we characterized two commonly used vascular models: native rat aorta and cultured human umbilical vein endothelial cell (HUVEC) monolayer. We determined heparin contents to be about 10,000 ng/cm2 on the native aorta, and about ten-fold lower on cultured HUVECs. Interestingly HUVECs demonstrated a five-fold lower anti-coagulation capacity in inactivating both Factor Xa and thrombin relative to native aortas. We verified the validity and accuracy of the novel assays developed in this work using LC-MS analysis. Conclusions Our assays are of high relevance in the vascular community as they can be utilized to establish the anti-thrombogenic capacity of many different types of surfaces such as vascular grafts and transplants. This work will also advance the capacity for glycocalyx-targeting therapeutics development to treat damaged vasculatures.

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Protease activity and the role of the endothelial glycocalyx in inflammation

Cited by 57 publications

References 75 publications

Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives

Association of impaired endothelial glycocalyx with arterial stiffness, coronary microcirculatory dysfunction, and abnormal myocardial deformation in untreated hypertensives

Heparan Sulfate Regrowth Profiles Under Laminar Shear Flow Following Enzymatic Degradation

New Functional Tools for Antithrombogenic Activity Assessment of Live Surface Glycocalyx

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