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How ischaemic preconditioning protects small liver grafts
Author(s) -
FrancoGou R,
RosellóCatafau J,
CasillasRamirez A,
MassipSalcedo M,
Rimola A,
Calvo N,
Bartrons R,
Peralta C
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1859
Subject(s) - medicine , ischemic preconditioning , cardiology , ischemia
Interleukin‐1 (IL‐1) and transforming growth factor‐β (TGFβ) are key inhibitors of hepatocyte proliferation after hepatectomy. IL‐1 inhibition by heat shock proteins (HSPs) has been reported in inflammatory processes. A recent study indicated the benefits of ischaemic preconditioning in reduced‐size orthotopic liver transplantation (ROLT). The present study examined: (a) the effect of ischaemic preconditioning on IL‐1 and TGFβ in ROLT; (b) whether preconditioning protects small liver grafts through HSP induction; and (c) whether the potential benefits of preconditioning on HSP is related to IL‐1 inhibition. Our results, obtained with an IL‐1 receptor antagonist, indicated the injurious effects of IL‐1 in ischaemia‐reperfusion (I/R) injury and established a relationship between IL‐1 and growth factors. Thus, IL‐1 reduced hepatocyte growth factor (HGF) and promoted TGFβ release, thus contributing to the impaired liver regeneration associated with ROLT. Preconditioning inhibited IL‐1 through nitric oxide (NO), thereby protecting against the injurious effects of IL‐1. In addition, by another pathway independent of NO, preconditioning induced HSP70 and haem‐oxygenase‐1 (HO‐1). HO‐1 protected against I/R injury and liver regeneration, whereas the benefits resulting from HSP70 were mainly related to hepatocyte proliferation. These results suggest a mechanism that explains the effectiveness of preconditioning in ROLT. They suggest, too, that other strategies, in addition to preconditioning, that modulate IL‐1 and/or HSPs could be considered in clinical situations requiring liver regeneration such as small liver grafts. Copyright © 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.