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Statins attenuate ischemia-reperfusion injury by inducing heme oxygenase-1 in infiltrating macrophages

Item Type:Article
Title:Statins attenuate ischemia-reperfusion injury by inducing heme oxygenase-1 in infiltrating macrophages
Creators Name:Gueler, F. and Park, J.K. and Rong, S. and Kirsch, T. and Lindschau, C. and Zheng, W. and Elger, M. and Fiebeler, A. and Fliser, D. and Luft, F.C. and Haller, H.
Abstract:Statins induce heme oxygenase-1 (HO-1) in several cell types, such as vascular smooth muscle cells, endothelial cells, and macrophages. The present study assessed the role of statin-induced HO-1 up-regulation on circulating monocytes/macrophages and their contribution in preventing renal ischemia-reperfusion (IR) injury in a rat model. Cerivastatin was administered via gavage (0.5 mg/kg) for 3 days before IR injury; controls received vehicle. Statin pretreatment reduced renal damage and attenuated renal dysfunction (P < 0.05) after IR injury. The protective statin pretreatment effect was completely abolished by cotreatment with tin protoporphyrin IX (Sn-PP), a competitive HO inhibitor. IR increased HO-1 expression at the transcript and protein level in renal tissue. This effect was significantly more evident (P < 0.05) in the statin-pretreated animals 24 hours after IR injury. We identified infiltrating macrophages as the major source of tissue HO-1 production. Moreover, in ancillary cell culture (monocyte cell line) and in in vivo experiments (isolation of circulating monocytes), we confirmed that statins regulate HO-1 expression in these cells. We conclude that statin treatment up-regulates HO-1 in circulating monocytes/macrophages in vivo and in vitro. We hypothesize that local delivery of HO-1 from infiltrating macrophages exerts anti-inflammatory effects after IR injury and thereby may reduce tissue destruction.
Keywords:Western Blotting, Tumor Cell Line, Cultured Cells, Enzymologic Gene Expression Regulation, Heme Oxygenase-1, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Macrophages, Confocal Microscopy, Monocytes, Protoporphyrins, Pyridines, Messenger RNA, Reperfusion Injury, Animals, Rats
Source:American Journal of Pathology
ISSN:0002-9440
Publisher:American Society for Investigative Pathology (U.S.A.)
Volume:170
Number:4
Page Range:1192-1199
Date:April 2007
Official Publication:https://doi.org/10.2353/ajpath.2007.060782
PubMed:View item in PubMed

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