• Rowan F van Golen, Megan J Reiniers, Nienke Vrisekoop, Coert J Zuurbier, Pim B Olthof, Jacco van Rheenen, Thomas M van Gulik, Barry J Parsons, and Michal Heger.
• 1 Department of Surgery, Surgical Laboratory, Academic Medical Center, University of Amsterdam , Amsterdam, The Netherlands .
• Antioxid. Redox Signal. 2014 Sep 1; 21 (7): 1098-118.

SignificanceHepatic ischemia/reperfusion (I/R) injury is an inevitable side effect of major liver surgery that can culminate in liver failure. The bulk of I/R-induced liver injury results from an overproduction of reactive oxygen and nitrogen species (ROS/RNS), which inflict both parenchymal and microcirculatory damage. A structure that is particularly prone to oxidative attack and modification is the glycocalyx (GCX), a meshwork of proteoglycans and glycosaminoglycans (GAGs) that covers the lumenal endothelial surface and safeguards microvascular homeostasis. ROS/RNS-mediated degradation of the GCX may exacerbate I/R injury by, for example, inducing vasoconstriction, facilitating leukocyte adherence, and directly activating innate immune cells.Recent AdvancesPreliminary experiments revealed that hepatic sinusoids contain a functional GCX that is damaged during murine hepatic I/R and major liver surgery in patients. There are three ROS that mediate GCX degradation: hydroxyl radicals, carbonate radical anions, and hypochlorous acid (HOCl). HOCl converts GAGs in the GCX to GAG chloramides that become site-specific targets for oxidizing and reducing species and are more efficiently fragmented than the parent molecules. In addition to ROS/RNS, the GAG-degrading enzyme heparanase acts at the endothelial surface to shed the GCX.Critical IssuesThe GCX seems to be degraded during major liver surgery, but the underlying cause remains ill-defined.Future DirectionsThe relative contribution of the different ROS and RNS intermediates to GCX degradation in vivo, the immunogenic potential of the shed GCX fragments, and the role of heparanase in liver I/R injury all warrant further investigation.

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