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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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