Tissue-specific effects of statins on the expression of heme oxygenase-1 in vivo
Section snippets
Materials and methods
Animals. Adult (6–8 weeks old) FVB transgenic mice, with the transgene comprising of the 15-kb HO-1 promoter driving expression of the reporter gene luciferase (luc), or HO-1-luc [35], were obtained from the Stanford Transgenic Animal Facility (Stanford, CA) and provided water and food ad libitum.
Reagents. Statins: simvastatin, lovastatin (EMD Biosciences, La Jolla CA), atorvastatin (Pfizer, New York, NY), and rosuvastatin (AstraZeneca, Wilmington DE) were dissolved in 30-μl Tween 80. The
HO activity
Fig. 1 and Table 1 show HO activity in the liver, brain, lung, and heart tissues 24 h after treatment with statins. After treatment with simvastatin, HO activity significantly increased 1.12-, 1.19-, and 1.70-fold in the liver, lung, and heart, respectively. No significant change in brain HO activity was observed following simvastatin treatment. Atorvastatin and rosuvastatin treatment resulted in similar significant increases in HO activity in the brain (1.06- and 1.16-fold), lung (1.11- and
Discussion
Pleiotropic mechanisms beyond the reduction of plasma cholesterol have been repeatedly shown to contribute to the anti-atherogenic and tissue-protective properties of statins. Based on previously published protocols and dosing regimens of statins administered to mice [42], [43], we first characterized the effects of four statins with varying structures and lipophilicities on in vivo HO activity. All four statins tested induced HO activity, but had varying tissue specificity profiles (Table 1).
Acknowledgments
This work was supported in part by National Institutes of Health Grant #HD58013, the Mary L. Johnson Research Fund, and the Christopher Hess Research Fund.
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