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

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Item Type:	Article
Title:	Statins attenuate ischemia-reperfusion injury by inducing heme oxygenase-1 in infiltrating macrophages
Creators Name:	Gueler, F., Park, J.K., Rong, S., Kirsch, T., Lindschau, C., Zheng, W., Elger, M., Fiebeler, A., Fliser, D., 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
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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