The mechanisms and physiological relevance of glycocalyx degradation in hepatic
ischemia/reperfusion injury
#MMPMID24313895
van Golen RF
; Reiniers MJ
; Vrisekoop N
; Zuurbier CJ
; Olthof PB
; van Rheenen J
; van Gulik TM
; Parsons BJ
; Heger M
Antioxid Redox Signal
2014[Sep]; 21
(7
): 1098-118
PMID24313895
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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.
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