期刊
ANTIOXIDANTS & REDOX SIGNALING
卷 21, 期 7, 页码 1098-+出版社
MARY ANN LIEBERT, INC
DOI: 10.1089/ars.2013.5751
关键词
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资金
- Academic Medical Center
- European Society of Anaesthesiology
- Dutch Organization for Scientific Research (NWO) [175.010.2007.00]
- Dutch Anti-Cancer Foundation (Stichting Nationaal Fonds Tegen Kanker) in Amsterdam
- Phospholipid Research Center in Heidelberg
- Nijbakker-Morra Foundation in Leiden
- Stichting Technologische Wetenschap (STW)
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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