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Glycocalyx and sepsis-induced alterations in vascular permeability.

Chelazzi C, Villa G, Mancinelli P, De Gaudio AR, Adembri C - Crit Care (2015)

Bottom Line: Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema.Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction.Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences, University of Florence, Section of Anesthesiology, Intensive Care and Pain Medicine, Viale Pieraccini, 6, 50139, Florence, Italy. cosimochelazzi@gmail.com.

ABSTRACT
Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

No MeSH data available.


Related in: MedlinePlus

Modification of glycocalyx components during sepsis. Representative light microphotograph of MAA (Maackia amurensis agglutinin) lectin histochemistry in mesoceacum of sham-operated (on the left side) and CLP (cecal ligation and puncture)-treated rats (on the right side) at 7 hours after surgery. In blue, MAA reactivity (indicating the presence of sialic acid linked α2,3 to galactose, arrows) was intense in mesoceacal vessels of sham operated rats (left side) and reduced in vessels of CPL rats (right side). Scale bar = 25 μm. Courtesy of Eleonora Sgambati.
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Fig3: Modification of glycocalyx components during sepsis. Representative light microphotograph of MAA (Maackia amurensis agglutinin) lectin histochemistry in mesoceacum of sham-operated (on the left side) and CLP (cecal ligation and puncture)-treated rats (on the right side) at 7 hours after surgery. In blue, MAA reactivity (indicating the presence of sialic acid linked α2,3 to galactose, arrows) was intense in mesoceacal vessels of sham operated rats (left side) and reduced in vessels of CPL rats (right side). Scale bar = 25 μm. Courtesy of Eleonora Sgambati.

Mentions: Localized or systemic inflammation leads to changes in structure and physiology of glycocalyx, inducing endothelial dysfunction (Figure 3). First and foremost, inflammation injury to glycocalyx is linked to increased paracellular permeability and outflow of albumin/fluid in the interstitial space through the ETCs [20]. Loss of anionic charges, changes in geometry of the clefts, and direct endothelial injury are responsible for this. Other observed changes in glycocalyx function during inflammation include loss of vascular tone with local blood pooling, degradation of heparan sulfate leading to a shift toward a pro-coagulant state with consequent micro-thrombosis, enhanced expression of adhesion molecules with increased leukocyte trafficking, and loss of antioxidative properties with progressive oxidative injury to the endothelium [15]. From an evolutionary and adaptive perspective, this local inflammatory response represents an active and structured response to tissue invasion by micro-organisms or unrecognized cells. In clinical syndromes of systemic inflammation, such as sepsis, major surgery, trauma, ischemia/reperfusion, and prolonged hyperglycemia, diffused and persistent alterations of glycocalyx are linked to widespread endothelial dysfunction, altered permeability, and impaired oxygen and nutrient delivery to cells [8,33,34]. There is experimental evidence that thickness and stiffness of endothelial glycocalyx are reduced by lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-α) exposure [35]. Clinically, these alterations are linked to loss of vascular tone, loss of albumin, hypovolemia, edema formation, and organ dysfunction [7]. Persistence of these alterations is associated with poor clinical outcome even if macrohemodynamic derangements have been corrected (see below). Furthermore, owing to the ubiquitous nature of the glycocalyx, its alterations lead to clinically relevant effects of inflammation also distant from primarily involved organs (that is, ‘organ cross-talk’ as in acute cardiorenal syndromes, where inflammatory injury to kidneys leads to inflammatory damage to endothelium) [36,37].Figure 3


Glycocalyx and sepsis-induced alterations in vascular permeability.

Chelazzi C, Villa G, Mancinelli P, De Gaudio AR, Adembri C - Crit Care (2015)

Modification of glycocalyx components during sepsis. Representative light microphotograph of MAA (Maackia amurensis agglutinin) lectin histochemistry in mesoceacum of sham-operated (on the left side) and CLP (cecal ligation and puncture)-treated rats (on the right side) at 7 hours after surgery. In blue, MAA reactivity (indicating the presence of sialic acid linked α2,3 to galactose, arrows) was intense in mesoceacal vessels of sham operated rats (left side) and reduced in vessels of CPL rats (right side). Scale bar = 25 μm. Courtesy of Eleonora Sgambati.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4308932&req=5

Fig3: Modification of glycocalyx components during sepsis. Representative light microphotograph of MAA (Maackia amurensis agglutinin) lectin histochemistry in mesoceacum of sham-operated (on the left side) and CLP (cecal ligation and puncture)-treated rats (on the right side) at 7 hours after surgery. In blue, MAA reactivity (indicating the presence of sialic acid linked α2,3 to galactose, arrows) was intense in mesoceacal vessels of sham operated rats (left side) and reduced in vessels of CPL rats (right side). Scale bar = 25 μm. Courtesy of Eleonora Sgambati.
Mentions: Localized or systemic inflammation leads to changes in structure and physiology of glycocalyx, inducing endothelial dysfunction (Figure 3). First and foremost, inflammation injury to glycocalyx is linked to increased paracellular permeability and outflow of albumin/fluid in the interstitial space through the ETCs [20]. Loss of anionic charges, changes in geometry of the clefts, and direct endothelial injury are responsible for this. Other observed changes in glycocalyx function during inflammation include loss of vascular tone with local blood pooling, degradation of heparan sulfate leading to a shift toward a pro-coagulant state with consequent micro-thrombosis, enhanced expression of adhesion molecules with increased leukocyte trafficking, and loss of antioxidative properties with progressive oxidative injury to the endothelium [15]. From an evolutionary and adaptive perspective, this local inflammatory response represents an active and structured response to tissue invasion by micro-organisms or unrecognized cells. In clinical syndromes of systemic inflammation, such as sepsis, major surgery, trauma, ischemia/reperfusion, and prolonged hyperglycemia, diffused and persistent alterations of glycocalyx are linked to widespread endothelial dysfunction, altered permeability, and impaired oxygen and nutrient delivery to cells [8,33,34]. There is experimental evidence that thickness and stiffness of endothelial glycocalyx are reduced by lipopolysaccharide (LPS) or tumor necrosis factor-alpha (TNF-α) exposure [35]. Clinically, these alterations are linked to loss of vascular tone, loss of albumin, hypovolemia, edema formation, and organ dysfunction [7]. Persistence of these alterations is associated with poor clinical outcome even if macrohemodynamic derangements have been corrected (see below). Furthermore, owing to the ubiquitous nature of the glycocalyx, its alterations lead to clinically relevant effects of inflammation also distant from primarily involved organs (that is, ‘organ cross-talk’ as in acute cardiorenal syndromes, where inflammatory injury to kidneys leads to inflammatory damage to endothelium) [36,37].Figure 3

Bottom Line: Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema.Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction.Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Health Sciences, University of Florence, Section of Anesthesiology, Intensive Care and Pain Medicine, Viale Pieraccini, 6, 50139, Florence, Italy. cosimochelazzi@gmail.com.

ABSTRACT
Endothelial cells line the inner portion of the heart, blood vessels, and lymphatic vessels; a basal membrane of extracellular matrix lines the extraluminal side of endothelial cells. The apical side of endothelial cells is the site for the glycocalyx, which is a complex network of macromolecules, including cell-bound proteoglycans and sialoproteins. Sepsis-associated alterations of this structure may compromise endothelial permeability with associated interstitial fluid shift and generalized edema. Indeed, in sepsis, the glycocalyx acts as a target for inflammatory mediators and leukocytes, and its ubiquitous nature explains the damage of tissues that occurs distant from the original site of infection. Inflammatory-mediated injury to glycocalyx can be responsible for a number of specific clinical effects of sepsis, including acute kidney injury, respiratory failure, and hepatic dysfunction. Moreover, some markers of glycocalyx degradation, such as circulating levels of syndecan or selectins, may be used as markers of endothelial dysfunction and sepsis severity. Although a great deal of experimental evidence shows that alteration of glycocalyx is widely involved in endothelial damage caused by sepsis, therapeutic strategies aiming at preserving its integrity did not significantly improve the outcome of these patients.

No MeSH data available.


Related in: MedlinePlus