Hyaluronidase Proof for Endothelial Glycocalyx as Partaker of Microcirculation Disturbances

Covalent modification of bovine testicular hyaluronidase with chondroitin sulphate led to changes in the pattern of glycation of native and modified enzyme in its reaction with neutral saccharides and N-acetylhexosamines. Thus, mono- and di-saccharides inactivated the native hyaluronidase to a greater extent than the chondroitin sulfate-modified enzyme. N-acetylhexosamine, on the opposite, inactivated the modified hyaluronidase to a greater extent than the native one. These properties made it possible to use native and modified hyaluronidase as an informative research system for in vivo measurement of the predominant type of saccharide agents in the circulation. The proposed approach was experimentally substantiated by obtained results of the study on these interactions of hyaluronidase derivatives with hyaluronan fragments and their mixture. In a model of post-ischemic perfusion of the rat limb, the effect of hyaluronidase derivatives and their components on restoration of the microcirculation were tracked using laser Doppler flowmetry. Native hyaluronidase accelerated the restoration of initial level of microcirculation, but modified enzyme was markedly inhibited by glycocalyx degradation products. N-acetylhexosamine was positioned at the reducing terminal of these products as a natural label for these glycocalyx fragments. These and other data obtained under various experimental conditions supported the participation of endothelial glycocalyx in microcirculation disturbances.

Resuscitation fluids as drugs:targeting the endothelial glycocalyx

Fluid resuscitation is an essential intervention in critically ill patients,and its ultimate goal is to restore tissue perfusion.Critical illnesses are often accompanied by glycocalyx degradation caused by inflammatory reactions,hypoperfusion,shock,and so forth,leading to disturbed microcirculatory perfusion and organ dysfunction.Therefore,maintaining or even restoring the glycocalyx integrity may be of high priority in the therapeutic strategy.Like drugs,however,different resuscitation fluids may have beneficial or harmful effects on the integrity of the glycocalyx.The purpose of this article is to review the effects of different resuscitation fluids on the glycocalyx.Many animal studies have shown that normal saline might be associated with glycocalyx degradation,but clinical studies have not confirmed this finding.Hydroxyethyl starch(HES),rather than other synthetic colloids,may restore the glycocalyx.However,the use of HES also leads to serious adverse events such as acute kidney injury and bleeding tendencies.Some studies have suggested that albumin may restore the glycocalyx,whereas others have suggested that balanced crystalloids might aggravate glycocalyx degradation.Notably,most studies did not correct the effects of the infusion rate or fluid volume;therefore,the results of using balanced crystalloids remain unclear.Moreover,mainly animal studies have suggested that plasma may protect and restore glycocalyx integrity,and this still requires confirmation by high-quality clinical studies.

Interaction of arterial proteoglycans with low density lipoproteins(LDLs):From theory to promising therapeutic approaches

Although atherosclerosis is a multifactorial process,proteoglycans mediated lipoprotein(LDL)retention at the subendothelial space is a necessary and sufficient event in provoking lesion initiation.Proteoglycans(PGs)are usually composed of one core protein backbone with one or more glycosaminoglycan chains(GAGs)covalently linked,mainly include perlecan,biglycan,versican,and decorin.The interaction between LDL and proteoglycans is apparently mediated by the basic amino acids in apoB-100,the moiety of LDL,electrostatic interacting with the negatively charged GAGs(sulfate or carbohydrate groups)of proteoglycans or though some bridge molecules like sphingomyelinase(SMase)or lipoprotein lipase(LpL).In the later section,we collate the promising therapeutic approaches that have been proposed up to now,targeting LDL-PGs interaction.It should be concluded that previous studies on interaction between LDL and PGs mainly focused on perlecan,biglycan,decorin,and versican that all located in the extracellular matrix(ECM),future studies should pay more attention to the endothelial surface glycocalyx and its interaction with LDLs,seeking promising therapeutic targets more specifically.