Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A<sub>2A</sub>receptor activation

Platts, Steven H.; Linden, Joel; Duling, Brian R.

doi:10.1152/ajpheart.00899.2002

Cited by 67 publications

(80 citation statements)

References 45 publications

(89 reference statements)

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“…Numerous studies have shown that the 70-kDa dextran does not penetrate the glycocalyx and is therefore retained in the vasculature, whereas the 40-kDa dextran penetrates the glycocalyx within minutes and may leave the vasculature (27,28,40). For permeability testing of the glycocalyx, use was made of this different behavior of both dextrans by examing the dextran concentration, normalized to the doses given, for the first 30 min after administration.…”

Section: Methodsmentioning

confidence: 99%

“…Recent evidence demonstrated a role of the glycocalyx in models of ischemiareperfusion injury, inflammation, and altered lipoprotein levels (26,28,38). To our knowledge, no study has examined whether hyperglycemia affects the glycocalyx.…”

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confidence: 99%

“…We tested this hypothesis by determining 1) glycocalyx permeability and volume by fluorescent-labeled dextrans of different molecular masses, which allow glycocalyx characterization (27,28,40); 2) lineal density of capillaries with flowing RBCs, visualized by the OPStechnique; and 3) stress-strain relations of RBC using LORCA. All experiments were performed in a recently developed, anesthetized and mechanically ventilated mouse model with stable hemodynamics (44).…”

mentioning

confidence: 99%

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Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells

Zuurbier

Demirci²,

Koeman³

et al. 2005

Journal of Applied Physiology

155

165

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Zuurbier, Coert J., Cihan Demirci, Anneke Koeman, Hans Vink, and Can Ince. Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells. J Appl Physiol 99: [1471][1472][1473][1474][1475][1476] 2005. First published July 14, 2005; doi:10.1152/japplphysiol.00436.2005.-Hyperglycemia is becoming recognized as an important risk factor for microvascular dysfunction. We hypothesized that short-term hyperglycemia, either on the scale of hours or weeks, alters the barrier function and the volume of the endothelial glycocalyx and decreases functional capillary density and deformability of the red blood cells (RBCs). All experiments were performed in anesthetized, mechanically ventilated, C57BL/6 mice that were either normoglycemic, acutely hyperglycemic (25 mM) for 60 min due to infusion of glucose, or hyperglycemic (25 mM) for 2-4 wk (db/db mice). The glycocalyx was probed using 40-kDa Texas red dextran, which is known to permeate the glycocalyx, and 70-kDa FITC dextran, which has impaired access to the glycocalyx in healthy animals. Clearance of the dye from the blood was measured. An orthogonal polarization spectral imaging technique was used to visualize the number of capillaries with flowing RBCs of the dorsal flexor muscle. The data indicate that short-term hyperglycemia causes a rapid decrease of the ability of the glycocalyx to exclude 70-kDa dextran. No change in the vascular permeation of 40-kDa dextran was observed. Glycocalyx volume was not affected by short-term hyperglycemia. In addition, 1 h of hyperglycemia resulted in a 38% decrease of the lineal density of capillaries with flowing RBCs. This decreased lineal density was not observed in the 2-to 4-wk hyperglycemia model. Short-term hyperglycemia was without any effect on the deformablity of the RBCs. The data indicate that the described increased vascular permeability with hyperglycemia can be ascribed to an increased permeability of the glycocalyx, identifying the glycocalyx as a potential early target of hyperglycemia. vascular permeability; diabetes; skeletal muscle; db/db mice HYPERGLYCEMIA, EITHER IN ITS acute form, such as which may occur in hospitalized critically ill patients, or in its chronic form, such as is present in patients with diabetes mellitus, is associated with increased rates of morbidity and mortality and diminished clinical outcome. The central importance of a vascular pathology underlying the hyperglycemia-associated poor prognosis is becoming increasingly evident. Characteristics of hyperglycemia-induced vasculopathy include decreased endothelium-dependent vasodilation, increased capillary permeability for large proteins such as albumin, swelling of endothelial cells, decreased capillary dimensions and diameters, and thickening of the basal lamina (5,13,20,23,33,41).The endothelial cell glycocalyx, a 0.2-to 0.5-m matrix lining the luminal surface of all blood vessels, is a significant factor in microvascular regulation by its action on volum...

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Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells

Zuurbier

Demirci²,

Koeman³

et al. 2005

Journal of Applied Physiology

155

165

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“…In animal studies, antioxidants rapidly reversed glycocalyx damage, including polyethylene glycol [46], NO [34], adenosine agonists [45], TNF-a inhibitors [43], allopurinol, heparin and hyaluronan [47]. These agents reduced oxidative stress, cellular transudate, glycocalyx shedding and restored glycocalyx volume.…”

Section: Damage To the Endothelial Surface Layermentioning

confidence: 98%

The endothelial glycocalyx: a review of the vascular barrier

Alphonsus¹,

2014

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SummaryThe endothelial glycocalyx is an important part of the vascular barrier. The glycocalyx is intimately linked to the homoeostatic functions of the endothelium. Damage to the glycocalyx precedes vascular pathology. In the first part of this paper, we have reviewed the structure, physiology and pathology of the endothelial glycocalyx, based on a literature search of the past five years. In the second part, we have systematically reviewed interventions to protect or repair the glycocalyx. Glycocalyx damage can be caused by hypervolaemia and hyperglycaemia and can be prevented by maintaining a physiological concentration of plasma protein, particularly albumin.

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“…Its properties, such as capillary barrier function and interaction with plasma components, have been studied (20). The glycocalyx consists of protein, glycolipid, and proteoglycans, including exposed charged groups, and also contains membranebound molecules, such as selectins and integrins (22, 25), involved in immune reactions and inflammatory processes (13,18,29).The intracellular uptake of macromolecules is possibly regulated by glycocalyx properties, such as surface charge and morphological barriers. The glycocalyx surface has a negative charge because the glycocalyx has some acidic mucopolysaccharide sidechains (GAG), which contain many carboxyl and sulfate groups.…”

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confidence: 99%

Effect of glycocalyx on shear-dependent albumin uptake in endothelial cells

Ueda

Shimomura

Ikeda

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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The glycocalyx layer on the surface of an endothelial cell is an interface barrier for uptake of macromolecules, such as low-density lipoprotein and albumin, in the cell. The shear-dependent uptake of macromolecules thus might govern the function of the glycocalyx layer. We therefore studied the effect of glycocalyx on the shear-dependent uptake of macromolecules into endothelial cells. Bovine aorta endothelial cells were exposed to shear stress stimulus ranging from 0.5 to 3.0 Pa for 48 h. The albumin uptake into the cells was then measured using confocal laser scanning microscopy, and the microstructure of glycocalyx was observed using electron microscopy. Compared with the uptake into endothelial cells under static conditions (no shear stress stimulus), the albumin uptake at a shear stress of 1.0 Pa increased by 16% and at 3.0 Pa decreased by 27%. Compared with static conditions, the thickness of the glycocalyx layer increased by 70% and the glycocalyx charge increased by 80% at a shear stress of 3.0 Pa. The albumin uptake at a shear stress of 3.0 Pa for cells with a neutralized (no charge) glycocalyx layer was almost twice that of cells with charged layer. These findings indicate that glycocalyx influences the albumin uptake at higher shear stress and that glycocalyx properties (thickness and charge level) are involved with the shear-dependent albumin uptake process. blood flow; shear stress; glycocalyx charge; glycocalyx thickness; in vitro model ATHEROSCLEROTIC LESIONS appear in regions of low shear stress in relatively large arteries, such as the carotid bifurcation and the coronary artery (3). Atherosclerosis is initiated by the uptake of low-density lipoprotein (LDL) (24), which is highly associated with hemodynamic stress. Some studies demonstrate that the transport of macromolecules such as albumin across the cell membrane is strongly affected by the shear stress on endothelial cells (17,27). Kudo et al. (11,12) measured the effect of shear stress on albumin uptake into endothelial cells in vitro and reported an increased uptake at lower shear stress and a decreased uptake at higher shear stress. However, the mechanism of this biphasic response of uptake remains unclear.The endothelial cell surface is characterized by various extracellular domains of membrane-bound molecules, the glycocalyx (20), which can sense the shear force of flowing blood (9, 15). Luft (14) visualized the endothelial glycocalyx layer in vitro using ruthenium red staining in an electron microscopic study and found that the glycocalyx layer is about 20 nm thick. Subsequent in vitro electron microscopic observations of the molecules revealed that the glycocalyx thickness is Ͻ100 nm (26). In vivo studies (19, 21) have revealed thicker glycocalyx layers ranging from 0.5 m to over 1.0 m. This difference in thickness is due to the preparation and staining techniques, which cause the collapse of the glycocalyx structures (14,20,32,33).The glycocalyx surface forms a complex three-dimensional array of soluble plasma components, including ...

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Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A_2Areceptor activation

Cited by 67 publications

References 45 publications

Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells

Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells

The endothelial glycocalyx: a review of the vascular barrier

Effect of glycocalyx on shear-dependent albumin uptake in endothelial cells

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Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A2Areceptor activation

Cited by 67 publications

References 45 publications

Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells

Short-term hyperglycemia increases endothelial glycocalyx permeability and acutely decreases lineal density of capillaries with flowing red blood cells

The endothelial glycocalyx: a review of the vascular barrier

Effect of glycocalyx on shear-dependent albumin uptake in endothelial cells

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Rapid modification of the glycocalyx caused by ischemia-reperfusion is inhibited by adenosine A_2Areceptor activation