Tissue-specific effects of statins on the expression of heme oxygenase-1 in vivo.
Heme oxygenase-1 (HO-1) plays a central role in antioxidant and anti-inflammatory actions, which may be mediated through its formation of biliverdin/bilirubin and carbon monoxide. HMG-CoA reductase inhibitors (statins) induce in vitro HO-1 expression and are reported to have pleiotropic benefits that reduce oxidative stress in the vasculature. We characterized the effects of statins on in vivo HO-1 expression in various extravascular tissues: liver, lung, brain, and heart. Adult mice were orally administered simvastatin, lovastatin, atorvastatin, or rosuvastatin. HO activity significantly increased in a statin- and tissue-specific manner, with all statins increasing heart and lung activity within 24 h. Significant elevations of HO-1 protein and mRNA were also observed in heart and lung after atorvastatin treatment. We conclude that in vivo HO-1 induction is statin- and tissue-specific. Through this pathway, statins may confer antioxidant and anti-inflammatory actions in the vasculature and extravascular systems.
Hsu
Mark
M
Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
Muchova
Lucie
L
Morioka
Ichiro
I
Wong
Ronald J
RJ
Schröder
Henning
H
Stevenson
David K
DK
D000818:Animals; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D012333:RNA, Messenger; D051547:Heme Oxygenase-1