The mechanisms and physiological relevance of glycocalyx degradation in hepatic ischemia/reperfusion injury

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, Michal Heger

Research output: Contribution to journal/periodicalArticleScientificpeer-review

Abstract

SIGNIFICANCE: Hepatic 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 ADVANCES: Preliminary 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 ISSUES: The GCX seems to be degraded during major liver surgery, but the underlying cause remains ill-defined.

FUTURE DIRECTIONS: The 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.

Original languageEnglish
Pages (from-to)1098-118
Number of pages21
JournalAntioxidants and Redox Signaling
Volume21
Issue number7
DOIs
Publication statusPublished - 01 Sep 2014

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