Rosuvastatin exerts favourable effects on thrombosis and neointimal growth in a mouse model of endothelial injury

 

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Summary

Apart from reducing systemic lipid levels, statins may improve the clinical course of atherosclerosis by exerting favourable pleiotropic effects on the vessel wall.We studied the effects of rosuvastatin, a new, potent 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on vascular remodelling after endothelial injury in the hyperlipidaemic apolipoprotein E-knockout (apoE-/-) mouse. ApoE-/- mice, 22-weeks-old, were injected daily with rosuvastatin at a low (1 mg/kg; n=27) or high dosage (10 mg/kg; n=24), or with vehicle alone (n=26).After treatment for 2 weeks,endothelial injury and thrombosis of the carotid artery was induced with 10% ferric chloride.Treatment was then resumed for a 3-week period.Although statin treatment did not affect the plasma lipid levels of mice, mean times to arterial thrombosis were prolonged in the low-dose and the high-dose group compared to controls (P<0.05 and P<0.01 respectively). Interestingly, rosuvastatin withdrawal 4 days before injury completely reversed the antithrombotic effects of the drug. In follow-up studies 3 weeks after injury,deposition of fibrin in the vessel wall was significantly reduced in the rosuvastatin-treated animals. There was an increase in the content of α -actin-positive smooth muscle cells (P =0.008) and collagen fibers (P<0.001), and a concomitant decrease in the number of oxLDL-containing macrophages (P<0.001). Overall, the neointimal area and the severity of luminal stenosis were significantly reduced in statin-treated mice. Thus, rosuvastatin attenuates arterial thrombosis and neointima formation, and it may stabilise vascular lesions developing after endothelial injury in mice.These effects are independent of systemic lipid lowering.

• References

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