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      The Role of Adipokines in Surgical Procedures Requiring Both Liver Regeneration and Vascular Occlusion

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          Abstract

          Liver regeneration is a perfectly calibrated mechanism crucial to increase mass recovery of small size grafts from living donor liver transplantation, as well as in other surgical procedures including hepatic resections and liver transplantation from cadaveric donors. Regeneration involves multiple events and pathways in which several adipokines contribute to their orchestration and drive hepatocytes to proliferate. In addition, ischemia-reperfusion injury is a critical factor in hepatic resection and liver transplantation associated with liver failure or graft dysfunction post-surgery. This review aims to summarize the existing knowledge in the role of adipokines in surgical procedures requiring both liver regeneration and vascular occlusion, which increases ischemia-reperfusion injury and regenerative failure. We expose and discuss results in small-for-size liver transplantation and hepatic resections from animal studies focused on the modulation of the main adipokines associated with liver diseases and/or regeneration published in the last five years and analyze future perspectives and their applicability as potential targets to decrease ischemia-reperfusion injury and improve regeneration highlighting marginal states such as steatosis. In our view, adipokines means a promising approach to translate to the bedside to improve the recovery of patients subjected to partial hepatectomy and to increase the availability of organs for transplantation.

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          Most cited references85

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          Liver regeneration after partial hepatectomy: critical analysis of mechanistic dilemmas.

          Liver regeneration after partial hepatectomy is one of the most studied models of cell, organ, and tissue regeneration. The complexity of the signaling pathways initiating and terminating this process have provided paradigms for regenerative medicine. Many aspects of the signaling mechanisms involved in hepatic regeneration are under active investigation. The purpose of this review is to focus on the areas still not well understood. The review also aims to provide insights into the ways by which current concepts of liver regeneration can provide understanding regarding malfunction of the regenerative process in liver diseases, such as acute liver failure.
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            Plasminogen activator inhibitor-1 (PAI-1): a key factor linking fibrinolysis and age-related subclinical and clinical conditions.

            The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a prothrombotic imbalance in the fibrinolysis homeostasis has been hypothesized as the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the result of the interactions among multiple plasminogen activators and inhibitors constituting the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Narrative review. Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urokinase-type plasminogen activator, the two plasminogen activators able to activate plasminogen. Current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker that may become a biological parameter to be progressively considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the future. © 2010 Blackwell Publishing Ltd.
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              Chemerin and its receptors in leukocyte trafficking, inflammation and metabolism.

              Chemerin was isolated as the natural ligand of the G protein-coupled receptor ChemR23. Chemerin acts as a chemotactic factor for leukocyte populations expressing ChemR23, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Chemerin is expressed by epithelial and non-epithelial cells as an inactive precursor, present at nanomolar concentrations in plasma. Processing of the precursor C-terminus is required for generating bioactive forms of chemerin. Various proteases mediate this processing, including neutrophil serine proteases and proteases from coagulation and fibrinolytic cascades. ChemR23-expressing cells are recruited in human inflammatory diseases, such as psoriasis and lupus. In animal models, both pro-inflammatory and anti-inflammatory roles of chemerin have been reported. Recently, two other receptors for chemerin were described, GPR1 and CCRL2, but their functional relevance is largely unknown. Both chemerin and ChemR23 are also expressed by adipocytes, and the emerging role of chemerin as an adipokine regulating lipid and carbohydrate metabolism is an area of intense research. Copyright © 2011 Elsevier Ltd. All rights reserved.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                30 October 2018
                November 2018
                : 19
                : 11
                : 3395
                Affiliations
                [1 ]Experimental Liver Surgery and Liver Transplantation, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), 08036 Barcelona, Spain; analvarezmercado@ 123456gmail.com (A.I.A.-M.); ebujaldonormaechea@ 123456gmail.com (E.B.)
                [2 ]Centro de Investigación Biomédica en Red de Enfermedades Hepáticas (CIBEREHD), 28029 Madrid, Spain; jordi.gracia@ 123456idibaps.org
                [3 ]Liver Vascular Biology Research Group, IDIBAPS, 08036 Barcelona, Spain
                [4 ]Facultad de Medicina, Universidad Internacional de Cataluña, 08017 Barcelona, Spain
                Author notes
                [* ]Correspondence: cperalta@ 123456clinic.ub.es ; Tel.: +34-932-275-400
                Author information
                https://orcid.org/0000-0002-8476-9970
                Article
                ijms-19-03395
                10.3390/ijms19113395
                6274984
                30380727
                a9b69f5c-fc1d-4b43-8687-3af6eed8daa4
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 30 August 2018
                : 26 October 2018
                Categories
                Review

                Molecular biology
                ischemic/reperfusion injury,liver regeneration,adipokines,partial hepatectomy

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