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Archive for February 24th, 2012

Statins inhibit thrombosis

24 Feb, 12 | by Alistair Lindsay

Hypercholesterolemia is one of the primary risk factors for atherosclerotic coronary disease. Statins have revolutionised lipid management with their proven ability to reduce circulating cholesterol levels and have even demonstrated regression of coronary plaques. Interestingly, statins have also been shown to have anti-inflammatory and anti-thrombotic activities, with several studies having shown statin therapy to be associated with a significant reduction in venous thromboembolism.  However, the mechanisms by which statins achieve this remain obscure.

In this basic science study Owens et al explore this question using a variety of pre-clinical models and human cells from patients with familial hypercholesterolemia (FH).  The authors demonstrate that hypercholesterolemia per se is associated with increased platelet reactivity and an increased tendency to thrombosis. The key factor appears to be oxidized low-density lipoprotein (oxLDL) particles which are present in the circulation of patients with coronary artery disease and also in patients with FH.  Elevated levels of oxLDL in plasma induces expression of the procoagulant protein tissue factor (TF) in monocytes. Genetic knockout of TF reduced coagulation despite hypercholesterolemia, consistent with a major role for monocyte-derived TF in the activation of coagulation. Furthermore, treatment with simvastatin was able to reduce levels of oxLDL, leading to reductions in monocyte TF expression and decreases in coagulation activation and inflammation even without significant reductions in total cholesterol.

Conclusions

Hypercholesterolemia induces a pro-thrombotic state through the actions of oxidised LDL particles on monocyte production of tissue factor.  Statins effectively inhibit this pathway and may be important in reducing atherothrombosis.

  • Owens AP 3rd, Passa m FH, Antoniak S, et al.  Monocyte tissue factor-dependent activation of coagulation in hypercholesterolemic mice and monkeys is inhibited by simvastatin.   J Clin Invest. 2012 Feb 1;122(2):558-68.

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