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Preview of articles to be published Jan. 3, 2012
Date:1/3/2012

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VASCULAR BIOLOGY

Link between hypercholesterolemia and blood clots can be broken by statins

High levels of cholesterol in the blood is very common, and can lead to hardening of arteries (atherosclerosis), the formation of plaques, and eventually the complete blockage of blood vessels. Hypercholesterolemia is also associated with a procoagulant state characterized by platelet hyperactivity. It has previously been shown that when LDL (the "bad cholesterol") is oxidized (forming oxLDL), it can induce an immune response and induce expression of the pro-coagulant protein tissue factor (TF) in monocytes/macrophages, endothelial cells, and smooth muscle cells. In new research, Nigel Mackman and colleagues, at the University of North Carolina at Chapel Hill, confirmed previous findings that high cholesterol results in a pro-coagulant state and activation of platelets in human patients. They then investigated the mechanism by which hypercholesterolemia leads to activation of coagulation. They found that genetic deficiency of TF in bone marrow cells reduced coagulation in hypercholesterolemic mice. Treatment of hypercholesterolemic mice and monkeys with the statin simvastatin, which inhibits TF expression in monocytes and macrophages, reduced oxLDL, monocyte TF expression, activation of coagulation, and inflammation without affecting total cholesterol levels. These results suggest that the pro-thrombotic state associated with hypercholesterolemia is caused by oxLDL-mediated induction of monocyte TF expression.

In the accompanying commentary, Roy Silverstein, of the Medical College of Wisconsin, explains these findings also provide a new understanding of statin action, and suggests that targeting this pathway could be useful in the treatment of thrombosis.

TITLE: Monocyte tissue factordependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by s
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Contact: Karen Honey
press_releases@the-jci.org
Journal of Clinical Investigation
Source:Eurekalert

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