on November 29, 2004
Published online before print November 29, 2004, doi: 10.1161/01.ATV.0000151647.14923.ec
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Submitted on October 4, 2004
Accepted on November 12, 2004
Statins and Blood Coagulation
Anetta Undas ;
From the Department of Medicine (A.U.), Jagiellonian University School of Medicine, Krakow, Poland; and the Department of Biochemistry (K.E.B.Z., K.G.M.), University of Vermont, Burlington.
* To whom correspondence should be addressed. E-mail: kenneth.mann{at}uvm.edu.
Abstract--The 3hydroxy3methylglutaryl (HMG)-coenzyme A (CoA) reductase inhibitors (statins) have been shown to exhibit several vascular protective effects, including antithrombotic properties, that are not related to changes in lipid profile. There is growing evidence that treatment with statins can lead to a significant downregulation of the blood coagulation cascade, most probably as a result of decreased tissue factor expression, which leads to reduced thrombin generation. Accordingly, statin use has been associated with impairment of several coagulant reactions catalyzed by this enzyme. Moreover, evidence indicates that statins, via increased thrombomodulin expression on endothelial cells, may enhance the activity of the protein C anticoagulant pathway. Most of the antithrombotic effects of statins are attributed to the inhibition of isoprenylation of signaling proteins. These novel properties of statins, suggesting that these drugs might act as mild anticoagulants, may explain, at least in part, the therapeutic benefits observed in a wide spectrum of patients with varying cholesterol levels, including subjects with acute coronary events.
Key words: statins • blood coagulation • thrombin • protein C
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