JACC: Old and new therapies combine to tackle atherosclerosis

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Futuristic nanotechnology has been teamed with a decades-old drug to beat atherosclerotic plaques in research conducted at Washington University School of Medicine in St. Louis and published in the September issue of the Journal of the American College of Cardiology: Cardiovascular Imaging

Scientists have found that drug-laced nanoparticles added to statin treatments could stop the growth of tiny blood vessels that feed arterial plaques. Researchers suggest that the dual treatment also prevents the vessels from restarting their growth, which could shrink or stabilize plaques.

Although the data were obtained in tests on rabbits, the investigators hope that a similar approach could help human patients with atherosclerosis.

The nanoparticles were coated with a substance that made them stick in growing blood vessels and with fumagillin, a potent compound that stops blood vessel growth.

“We saw that statins sustain the acute inhibition of blood vessel growth produced by the fumagillin nanoparticles within the plaque," said senior author Gregory Lanza, MD, PhD, a Washington University cardiologist at Barnes Jewish Hospital in St. Louis.

“Our past research showed that fumagillin nanoparticles reduced blood vessel formation at the site of arterial plaques in experimental rabbits after one week,” Lanza said. “In this study, we tested how long that effect lasts and if it could be extended by statins.”

The rabbits used in the study ate a high-fat diet that caused arterial plaques. The researchers detected new blood vessel buildup at the site of plaques by coating nanoparticles that were targeted to neovessels with an MRI contrast agent.

When the rabbits received a single dose of blood-vessel-targeted nanoparticles that also carried fumagillin, the researchers saw that the amount of MRI signal at the sites of plaques decreased about five-fold by the end of one week. But a high MRI signal returned by the fourth week, indicating that plaques were active again.

Because repeated injections of fumagillin nanoparticles are impractical for treating human patients, the researchers looked for an alternative method.

Atherosclerotic rabbits that got daily doses of the statin atorvastatin (Pfizer’s Lipitor) had no change in plaque angiogenesis measured by MRI. When the statin and the fumagillin nanoparticles were started at the same time, the atorvastatin had no additional benefits over the targeted therapy.

However, when the statin was given for at least one month prior to the fumagillin treatment, the five-fold reduction in MRI signal due to diminished neovessels was maintained for four weeks.

Lanza said that the results suggest that one or possibly two injections of nanoparticles in patients who are already on statins could lead to a long-term reduction in plaque activity and prolonged plaque stability. The results also illustrate the potential clinical use of MRI molecular imaging with the neovessel-targeted nanoparticles to measure plaque status in high-risk patients before clinical symptoms appear.

The nanoparticle technology permits potent therapeutics to be effective at minute doses by targeting them directly to the disease site. Moreover, MRI molecular imaging with the nanoparticles could be used to noninvasively monitor and manage the response to treatment and the progression of atherosclerotic disease.