Abstract | BACKGROUND AND PURPOSE: METHODS: To test this hypothesis, we treated 129/SV mice with atorvastatin (10 mg/kg) for 14 days and then withdrew treatment. RESULTS: Treatment with atorvastatin conferred stroke protection by 40% after filamentous occlusion of the middle cerebral artery followed by reperfusion. Withdrawal of statin treatment, however, resulted in the loss of stroke protection after 2 and 4 days. In mouse aortas and brain vasculature, statins upregulated eNOS message 2.3- and 1.7-fold, respectively, as measured by reverse transcription-polymerase chain reaction. Withdrawal of statins resulted in 5- and 2.7-fold downregulation of eNOS in aorta and brain, respectively, after 2 days. Statin treatment decreased RhoA GTPase membrane expression to 48%, while withdrawal of statins resulted in 4-fold increase of RhoA in the membrane. Moreover, platelet factor 4 and beta-thromboglobulin in plasma were significantly downregulated by statin treatment, but withdrawal of statins resulted in a 2.9- and 3.1-fold upregulation after 2 days, respectively. Thrombus formation induced by ligature of the inferior vena cava was significantly reduced by statin treatment. When statin treatment was withdrawn, however, protection was lost between 2 and 4 days. CONCLUSIONS: Acute termination of statin treatment results in a rapid loss of protection in mouse models of cerebral ischemia and thrombus formation independent of lipid lowering. In patients with acute or impending stroke, withdrawal of statins may impair outcome.
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Authors | Karen Gertz, Ulrich Laufs, Ute Lindauer, Georg Nickenig, Michael Böhm, Ulrich Dirnagl, Matthias Endres |
Journal | Stroke
(Stroke)
Vol. 34
Issue 2
Pg. 551-7
(Feb 2003)
ISSN: 1524-4628 [Electronic] United States |
PMID | 12574574
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Heptanoic Acids
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
- Pyrroles
- RNA, Messenger
- Atorvastatin
- Nitric Oxide Synthase
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Nos3 protein, mouse
- rhoA GTP-Binding Protein
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Topics |
- Animals
- Aorta
(enzymology, pathology)
- Atorvastatin
- Bleeding Time
- Blood Coagulation
(drug effects)
- Brain
(blood supply, enzymology, pathology)
- Brain Ischemia
(chemically induced, prevention & control)
- Disease Models, Animal
- Drug Administration Schedule
- Heptanoic Acids
(adverse effects, pharmacology)
- Hydroxymethylglutaryl-CoA Reductase Inhibitors
(adverse effects, pharmacology)
- Ligation
- Mice
- Nitric Oxide Synthase
(genetics, metabolism)
- Nitric Oxide Synthase Type II
- Nitric Oxide Synthase Type III
- Platelet Activation
(drug effects)
- Pyrroles
(adverse effects, pharmacology)
- RNA, Messenger
(metabolism)
- Stroke
(chemically induced, prevention & control)
- Substance Withdrawal Syndrome
- Vena Cava, Inferior
- Venous Thrombosis
(chemically induced, pathology)
- rhoA GTP-Binding Protein
(metabolism)
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