Nanoparticle Therapy Reduces Plaque Inflammation and Lowers Risk of Heart Attack or Stroke

Reconstituted HDL (high-density lipoprotein) nanoparticles were used to transport inflammation-retarding statins to atherosclerotic plaques where the drug acted to reduce arterial blockage that could cause heart attack or stroke.

Inflammation is a key feature of atherosclerosis and a target for therapy. While statins are known to have potent anti-inflammatory properties, they cannot be exploited fully as an oral statin therapy due to low systemic bioavailability.

Investigators at Mount Sinai School of Medicine (New York, NY, USA) sought to concentrate the anti-inflammatory benefits of statins by incorporating them into nanoparticles that would accumulate at sites of inflammation within the blood vessels. For this purpose, they designed an injectable reconstituted high-density lipoprotein (rHDL) nanoparticle carrier vehicle capable of delivering statins directly to atherosclerotic plaques.

They reported in the January 20, 2014, online edition of the journal Nature Communications that they had initially demonstrated the anti-inflammatory effect of statin-rHDL in vitro and showed that this effect was mediated through the inhibition of the mevalonate pathway. They also applied statin-rHDL nanoparticles in vivo in an apolipoprotein E-knockout mouse model of atherosclerosis and showed that the nanoparticles accumulated in atherosclerotic lesions in which they directly affected plaque macrophages. Finally, they demonstrated that a three-month low-dose statin-rHDL treatment regimen inhibited plaque inflammation progression, while a one-week high-dose regimen markedly decreased inflammation in advanced atherosclerotic plaques.

“Not only could the HDL nanotherapy potentially avert repeat heart attacks, it may also have the power to reduce recurrent strokes caused by clots in brain arteries, ” said senior author, Dr. Willem Mulder, associate professor of radiology at Mount Sinai School of Medicine. “We envision that a safe and effective HDL nanotherapy could substantially lower cardiovascular events during the critical period of vulnerability after a heart attack or stroke. While we have much more to do to confirm clinical benefit in patients, our study shows how this nanotherapy functions biologically, and how this novel concept could potentially also work in the clinical setting to solve a critical problem. This nanotherapy would be the first of its kind.”

The optimum use for HDL-statin nanotherapy would be by injection following treatment of an arterial clot. The HDL nanoparticle would deliver the statin directly to macrophages that are driving the inflammatory response. “This could potentially and very rapidly stabilize a dangerous situation,” said Dr. Mulder. “In addition, after discharge, patients would continue to use their oral statins to control LDL in their blood.”

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