Combined Nanoparticle and Statin Therapy Eliminates Atherosclerotic Plaques

Investigators at the Washington University School of Medicine (St. Louis, MO, USA) worked with a line of rabbits that became hyperlipidemic and developed atherosclerotic plaques when fed a high fat diet. The experimental therapy to treat this condition comprised paramagnetic nanoparticles coated with the antiangiogenic drug fumagillan. In some experiments, treatment with the nanoparticles was combined with the administration of the cholesterol-lowering statin atorvastatin. Cardiac magnetic resonance (CMR) molecular imaging was used to monitor the effectiveness of the treatment.

Results were published in the September 15, 2008, issue of the Journal of the American College of Cardiology (JACC): Cardiovascular Imaging. They showed that in a first experiment the fumagillin nanoparticles alone reduced plaque sizes by 50% to 75% after one week and maintained this effect for three weeks regardless of diet or drug dose. In the second study, atherosclerotic rabbits receiving statin alone had no antiangiogenic benefit after eight weeks. The nanoparticles decreased aortic angiogenesis for three weeks as in the first study, and re-administration on week four reproduced the three-week antiangiogenic response with no carry-over benefit. However, atorvastatin and two doses of fumagillin nanoparticles (at zero and four weeks) achieved marked and sustainable antiangiogenesis. Microscopic studies corroborated the high correlation between CMR signal and plaque size.

"Our past research showed that fumagillin nanoparticles reduced blood vessel formation at the site of arterial plaques in experimental rabbits after one week,” explained senior author Dr. Gregory Lanza, professor of medicine and biomedical engineering at Washington University School of Medicine. "In this study, we tested how long that effect lasts and if it could be extended by statins. We saw that statins sustain the acute inhibition of blood vessel growth produced by the fumagillin nanoparticles within the plaque.

Because nearly half of patients experiencing their first heart attack die soon after, our goal is to prevent or greatly delay clinically significant atherosclerotic disease. We hope to achieve this by a personalized nanomedicine approach that risk-stratifies patients and affords safe, targeted delivery of potent compounds that block progression in high-risk patients. This would be followed by management of the disease with standard-of-care drugs and periodic MRI monitoring of disease progression. We plan to conduct clinical trials to test this idea.”

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