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

Katrin Schäfer; Kilian Kaiser; Stavros Konstantinides

doi:10.1160/TH04-07-0415

Thrombosis and Haemostasis, Table of Contents

Thromb Haemost 2005; 93(01): 145-152
DOI: 10.1160/TH04-07-0415

Endothelium and Vascular Development

Schattauer GmbH

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

Katrin Schäfer

¹Department of Cardiology and Pulmonary Medicine, Georg August University of Goettingen, Goettingen, Germany

,

Kilian Kaiser

¹Department of Cardiology and Pulmonary Medicine, Georg August University of Goettingen, Goettingen, Germany

,

Stavros Konstantinides

¹Department of Cardiology and Pulmonary Medicine, Georg August University of Goettingen, Goettingen, Germany

› Author Affiliations

Abstract

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.

Keywords

Animal models - atherosclerosis - tissue remodelling - fibrinogen / fibrin - restenosis

Full Text

References

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