Rosuvastatin prevents endothelial cell death and reduces atherosclerotic lesion formation in ApoE-deficient mice

Accumulating evidence suggests that statins have beneficial effects which are independent of their lipid-lowering actions, on vascular cells. Here, we investigated whether the HMG-CoA reductase inhibitor rosuvastatin can inhibit atherosclerotic lesion development with favorable effects on endothelial cells in ApoE-deficient mice. Rosuvastatin rapidly phosphorylated Akt and endothelial nitric oxide synthase ( eNOS) in human endothelial cells. Endothelial cell death induced by serum starvation was significantly inhibited by rosuvastatin ( percent cell death; 45.9 +/- 2.4% vs. 37.3 +/- 1.1%, p < 0.05). Eight-week-old ApoE-deficient mice were orally administered vehicle or rosuvastatin at a dose of 20 mg/kg/day for 24 weeks. There was no significant difference in cholesterol profile. Rosuvastatin preserved endothelial lining at the aortic root (CD31-positive luminal side; 63.8 +/- 2.8% vs. 81.7 +/- 3.9%, p < 0.05). En face Sudan IV staining of aorta revealed that rosuvastatin significantly decreased the atherosclerotic area (21.9 +/- 2.9% vs. 11.9 +/- 1.9%, p < 0.05). Lipid deposition at the atherosclerotic area was also suppressed by rosuvastatin with more stabilized morphologic features as determined by oil red O staining (3.4 +/- 0.4% vs. 1.7 +/- 0.4%, p < 0.05). Our findings indicate that rosuvastatin protects endothelial cells from death with phosphorylation of Akt and eNOS. These effects may contribute, at least in part, to the anti-atherosclerotic effects of rosuvastatin. (C) 2007 Elsevier Masson SAS. All rights reserved.