Statins Help Lower Risk of Atherosclerosis by Reducing the Size of Arterial Plaques

Statins, a class of drugs that help reduce risk of atherosclerosis by lowering levels of low-density lipoproteins (LDL), also decrease the size of arterial plaques by stimulating macrophage emigration.

Investigators at New York University (NY, USA) worked with a novel mouse-transplant model of atherosclerosis regression in which aortic segments from diseased donors were placed into recipients with normal cholesterol levels. With this model they had previously shown that the induction of a chemokine receptor CCR7(C-C chemokine receptor type 7)-dependent emigration process triggered the rapid loss of CD68+ cells (mainly macrophages) from arterial plaques.

In the current study, the investigators examined the effect of statins on macrophage emigration from plaques. They reported in the December 6, 2011, online edition the journal PLoS One that when mice that had been genetically engineered to lack the gene for apolipoprotein E were fed a western diet-fed while being treated with either atorvastatin or rosuvastatin they experienced a substantial reduction in the CD68+ cell content in the plaques despite continued hyperlipidemia. There was a significant increase in CCR7 mRNA in CD68+ cells from both atorvastatin and rosuvastatin treated mice associated with emigration of CD68+ cells from plaques. Mice that lacked both the gene for apolipoprotein E and the gene for CCR7 failed to display a reduction in CD68+ cell content upon statin treatment.

The results of this study indicate that statins, in addition to their traditionally considered effects on atherosclerosis by retarding plaque progression through lowering LDL-cholesterol, may also have additional clinical benefits by accelerating plaque regression through enhancing CCR7 expression and emigration of CD68+ macrophages. These beneficial effects would have been missed if changes in plaque size had been the sole criterion of success.

“Our experimental findings indicate that statins, in addition to lowering LDL cholesterol, have clinical benefits of accelerating plaque regression by a newly discovered mechanism,”said senior author Dr, Michael Garabedian, professor of microbiology and urology at New York University. “It is possible that these drugs could possibly be more beneficial to a wider population of patients potentially reducing the overall lifetime burden of plaque and the prevention of atherosclerosis.”

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