[HMG-CoA reductase inhibitor and risk of stroke].
HMG-CoA reductase inhibitors are potent cholesterol-lowering drugs. Recent clinical trials and meta-analyses show a 30% stroke reduction after treatment with HMG-CoA reductase inhibitors. Subgroup analyses and experimental findings support the notion that HMG-CoA reductase inhibitors improve endothelial function directly by mechanism(s) independent of cholesterol-lowering. They reduce inflammatory, proliferative and thrombogenic processes in atherosclerotic plaques and improve endothelial dysfunction. Recent findings demonstrate an enhanced production of endothelium-derived nitric oxide (NO) by HMG-CoA reductase inhibitors. Endothelial NO is an important vasodilator and plays a beneficial role in cerebral ischemic injury. Prophylactic treatment with HMG-CoA reductase inhibitors in mice selectively upregulates endothelial NO synthase expression and activity, increases cerebral blood flow at resting state and during ischemia, and reduces cerebral infarct size after experimental stroke. These findings provide a novel mechanism for the prophylactic treatment of ischemia-induced cerebral injury under non-hypercholesterolemic conditions.
Neurologische Klinik, Medizinische Universität zu Lübeck.
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D000818:Animals; D001921:Brain / Q000098:blood supply; D002561:Cerebrovascular Disorders / Q000097:blood / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D051379:Mice; D019001:Nitric Oxide Synthase / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D019001:Nitric Oxide Synthase
HMG-CoA-Reduktasehemmer und Schlaganfallrisiko.