期刊
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
卷 25, 期 3, 页码 598-603出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1161/01.ATV.0000157145.98200.55
关键词
inflammation; statins; rats; brain ischemia; proteome; rosuvastatin; simvastatin; stroke-prone rats
Objective - Brain abnormalities, preceded by a systemic inflammation, develop in spontaneously hypertensive stroke-prone rats (SHRSP). In this model, we investigated whether the hydrophilic statin, rosuvastatin, influences the development of inflammation associated with brain abnormalities. Because differences in hydrophilicity/hydrophobicity contribute to the differences in statin pharmacology, we also evaluated the effects of simvastatin, a lipophilic molecule. Methods and Results - SHRSP, fed a high-salt diet, were treated long-term with vehicle or rosuvastatin (1 and 10 mg/kg per day). Brain abnormalities developed after 40 +/- 5 days and after 60 +/- 5 days of salt loading, in vehicle-treated and in rosuvastatin-treated (1 mg/kg per day) SHRSP, respectively. After 100 days of treatment, no damage was detectable in 30% of the rats treated with the highest dose of the drug. In comparison with vehicle-treated SHRSP, rosuvastatin treatment attenuated the transcription of monocyte chemoattractant protein-1, transforming growth factor-beta1, IL-1beta, and tumor necrosis factor-alpha in the kidney, and of P-selectin in brain vessels and increased the transcription of endothelial nitric oxide synthase mRNA in the aorta. Urinary excretion of acute-phase proteins increased with time in vehicle-treated animals but remained negligible in drug-treated animals. These effects are independent of changes in physiological parameters. Treatment of SHRSP with simvastatin (2 to 20 mg/kg per day) did not exert any protective effect. Conclusions - Rosuvastatin attenuates inflammatory processes associated with cerebrovascular disease.
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