Glycocalyx and sepsis-induced alterations in vascular permeability

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.

Therapeutic Restoration of Endothelial Glycocalyx in Sepsis

“…This conclusion is further supported by the finding that SDX has a beneficiary effect in the LPS-induced model of sepsis, which bypasses micro-organismal installation. On the other hand, a significant increase in sepsisrelated vascular permeability (Chelazzi et al, 2015) is curtailed by SDX. Although SDX is credited with anti-inflammatory and antithrombotic actions (Hoppensteadt and Fareed, 2014), it is likely that correction of vascular permeability is related to the It has been previously demonstrated that glycocalyx of endothelial cells and erythrocytes is impaired in the in vitro flow system when one of the cellular components has lost glycocalyx integrity (Oberleithner, 2013).…”

Renal Hemodynamics in AKI

“…55 Another emerging possibility to act therapeutically on endothelial vascular integrity involves Toll-like receptor 4-dependent activation of endothelial cells 56 and modulation thrombomodulindriven pathways. 57 From the long-term perspective, postinsult recovery of the peritubular capillary network may prevent chronic tubulointestinal hypoxia and fibrosis.…”

Skysčių skyrimas operacijos metu sepsiu sergančiam pacientui

“…Vienas pagrindinių veiksnių, sukeliančių šį skirtumą -sepsio metu aktyvintų uždegiminių ir priešuždegiminių mediatorių, bakterijų endotoksinų sukeltas endotelio pažeidimas ir glikokalikso vientisumo pažeidimas. Šis pažeidimas sukelia endotelio pralaidumą ir su tuo susijusį skysčių persiskirstymą bei intersticinės edemos formavimąsi [7]. Patologinį skysčio perėjimą sukelia ne tik minėtas mechanizmas, bet ir operacijos metu atliekamos chirurginės manipuliacijos, didinančios baltymų perėjimą iš kraujagyslės į tarpląstelinį tarpą, reperfuzinė pažaida, silpninanti kraujagyslinį barjerą, bei jatrogeninė hipervolemija, galinti sukelti glikokalikso pažeidimą, dėl kurio skysčiai ir baltymai pereina į ekstravaskulinį tarpą [8].…”