Microvascular and capillary perfusion following glycocalyx degradation

Cabrales, Pedro; Vázquez, Beatriz Y. Salazar; Tsai, Amy G.; Intaglietta, Marcos

doi:10.1152/japplphysiol.01155.2006

Cited by 101 publications

(120 citation statements)

References 33 publications

(56 reference statements)

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“…39,41,45 In addition to the tight junctions in between endothelial cells, the SGL plays an important role in maintaining the barrier function of endothelium due to its matrix-like structure as well as the charge. 1,9,11,18,39,44 Yuan et al 46 found that the permeability of intact rat pial microvessels to positively charged ribonuclease was four times as large as that to negatively charged a-lactalbumin, though they have almost the same size. Combining these measured permeability data with a mathematical model, they predicted that the charge density is~30 mEq/L in the structural components of the BBB, i.e., the SGL and the basement membrane.…”

Section: Introductionmentioning

confidence: 99%

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Yuan

2010

Ann Biomed Eng

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Abstract-Charge carried by the surface glycocalyx layer (SGL) of the cerebral endothelium has been shown to significantly modulate the permeability of the blood-brain barrier (BBB) to charged solutes in vivo. The cultured monolayer of bEnd3, an immortalized mouse cerebral endothelial cell line, is becoming a popular in vitro BBB model due to its easy growth and maintenance of many BBB characteristics over repeated passages. To test whether the SGL of bEnd3 monolayer carries similar charge as that in the intact BBB and quantify this charge, which can be characterized by the SGL thickness (L f ) and charge density (C mf ), we measured the solute permeability of bEnd3 monolayer to neutral solutes and to solutes with similar size but opposite charges: negatively charged a-lactalbumin (À11) and positively charged ribonuclease (+3). Combining the measured permeability data with a transport model across the cell monolayer, we predicted the L f and the C mf of bEnd3 monolayer, which is~160 nm and~25 mEq/L, respectively. We also investigated whether orosomucoid, a plasma glycoprotein modulating the charge of the intact BBB, alters the charge of bEnd3 monolayer. We found that 1 mg/mL orosomucoid would increase SGL charge density of bEnd3 monolayer to~2-fold of its control value.

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Section: Introductionmentioning

confidence: 99%

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Yuan

2010

Ann Biomed Eng

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“…As shown therein, no significant change in arteriolar or venular hematocrit occurred with fMLP, as assessed by direct spectrophotometric methods. In contrast, H CAP was found to increase in response to degradation of the glycocalyx twofold with direct infusion of heparinase with micropipettes (13) and systemic infusion of hyaluronidase (7). Systemic infusion of oxidized LDL increased it twofold (10), and sustained epifluorescence illumination increased it by 68% (59), presumably due to generation of reactive oxygen species in both studies.…”

Section: Discussionmentioning

confidence: 97%

“…Experimental manipulations of the structure of the glycocalyx by perfusion of the microvasculature with heparinase have revealed decreases in intravascular resistance to flow (50). Increases in capillary hematocrit (H CAP ) have been attributed to removal of the glycocalyx in response to perfusion with heparinase (13) and hyaluronidase (7) and the presence of reactive oxygen species derived from oxidized low-density lipoprotein (LDL) (10). Thus the structure of the glycocalyx is a prime determinant of numerous physiological and hemodynamic processes, and maintenance of its stability may preclude the onset of many pathological disturbances (5).…”

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confidence: 99%

Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation

Lipowsky

Gao

Lescanic

2011

American Journal of Physiology-Heart and Circulatory Physiology

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Lipowsky HH, Gao L, Lescanic A. Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation. Am J Physiol Heart Circ Physiol 301: H2235-H2245, 2011. First published September 16, 2011 doi:10.1152/ajpheart.00803.2011The endothelial glycocalyx has been identified as a barrier to transvascular exchange of fluid, macromolecules, and leukocyte-endothelium [endothelial cell (EC)] adhesion during the inflammatory process. Shedding of glycans and structural changes of the glycocalyx have been shown to occur in response to several agonists. To elucidate the effects of glycan shedding on microvascular hemodynamics and capillary resistance to flow, glycan shedding in microvessels in mesentery (rat) was induced by superfusion with 10 Ϫ7 M fMLP. Shedding was quantified by reductions of fluorescently labeled lectin (BS-1) bound to the EC and reductions in thickness of the barrier to infiltration of 70-kDa dextran on the EC surface. Red cell velocities (two-slit technique), pressure drops (dual servo-null method), and capillary hematocrit (direct cell counting) were measured in parallel experiments. The results indicate that fMLP caused shedding of glycans in all microvessels with reductions in thickness of the barrier to 70-kDa dextran of 110, 80, and 123 nm, in arterioles, capillaries, and venules, respectively.

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“…Loss of endothelial glycocalyx integrity after ischemia and reperfusion has been observed in experimental models (8,24,27) and in patients undergoing aortic surgery (28). Degradation of the endothelial glycocalyx by infusion of hyaluronidase causes capillary perfusion defects in rodents (7). Taken together, ischemic injury to endothelial cells and glycocalyx of peritubular capillaries may play a major role in the pathophysiology of acute kidney injury by reducing tissue perfusion and propagating inflammation in the reperfused kidney.…”

mentioning

confidence: 99%

Acute ischemic injury to the renal microvasculature in human kidney transplantation

Snoeijs¹,

Vink²,

Voesten³

et al. 2010

American Journal of Physiology-Renal Physiology

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Increased understanding of the pathophysiology of ischemic acute kidney injury in renal transplantation may lead to novel therapies that improve early graft function. Therefore, we studied the renal microcirculation in ischemically injured kidneys from donors after cardiac death (DCD) and in living donor kidneys with minimal ischemia. During transplant surgery, peritubular capillaries were visualized by sidestream darkfield imaging. Despite a profound reduction in creatinine clearance, total renovascular resistance of DCD kidneys was similar to that of living donor kidneys. In contrast, renal microvascular perfusion in the early reperfusion period was 42% lower in DCD kidneys compared with living donor kidneys, which was accounted for by smaller blood vessel diameters in DCD kidneys. Furthermore, DCD kidneys were characterized by smaller red blood cell exclusion zones in peritubular capillaries and by greater production of syndecan-1 and heparan sulfate (main constituents of the endothelial glycocalyx) compared with living donor kidneys, providing strong evidence for glycocalyx degradation in these kidneys. We conclude that renal ischemia and reperfusion is associated with reduced capillary blood flow and loss of glycocalyx integrity. These findings form the basis for development of novel interventions to prevent ischemic acute kidney injury. ischemia-reperfusion injury; endothelial glycocalyx KIDNEY TRANSPLANTATION IS inevitably associated with ischemia and reperfusion injury. Depending on the severity of injury, 20 -80% of recipients of deceased donor kidneys require dialysis treatment in the first week after transplantation, which is referred to as delayed graft function (26). This condition complicates patient management and is associated with a 40% increased rate of graft loss in kidneys from donors after brain death (45). Liberal use of donations after cardiac death greatly expands the number of available donor kidneys and may even eliminate transplant waiting lists (37). However, kidneys from these donors suffer extensive ischemic injury from circulatory arrest until organ preservation, which almost invariably leads to delayed graft function after transplantation. More importantly, up to 15-25% of these kidneys will never regain function, unnecessarily exposing recipients to the risks of major surgery and immunological sensitization (43).Adequate reperfusion is essential for functional recovery of donor kidneys and prevents ongoing ischemic tissue injury after revascularization. In rodent models of ischemic acute kidney injury, it has been demonstrated that the peritubular microcirculation suffers endothelial injury and functional impairment after reperfusion (5, 44), which has recently been observed in humans as well (13,21,31). The endothelium is covered by the glycocalyx, a dynamic network of proteoglycans and glycoproteins that determines vascular permeability, transduces shear stress to the endothelium, and prevents interaction of leukocytes and platelets with the vascular wall (29). Loss of endothel...

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Microvascular and capillary perfusion following glycocalyx degradation

Cited by 101 publications

References 33 publications

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Effect of Surface Charge of Immortalized Mouse Cerebral Endothelial Cell Monolayer on Transport of Charged Solutes

Shedding of the endothelial glycocalyx in arterioles, capillaries, and venules and its effect on capillary hemodynamics during inflammation

Acute ischemic injury to the renal microvasculature in human kidney transplantation

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