"Our past research showed that fumagillin nanoparticles reduced blood vessel formation at the site of arterial plaques in experimental rabbits after one week," says Lanza. "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 is impractical for treating human patients, the researchers looked for a way to extend the initial effectiveness.
Atherosclerotic rabbits that got daily doses of the statin atorvastatin (brand name Lipotor) 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 had been 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 says 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 nanoparticle
|Contact: Gwen Ericson|
Washington University School of Medicine