New therapy halts artery plaque growth and suppresses inflammation
According to the CDC, 1 in 4 deaths are due to heart attacks. In fact it is the leading cause of death for both men and women. Largely attributed to diet, most medications solely aim at lowering cholesterol. However, a research team showed that a nanotherapeutic medicine can halt the growth of artery plaque cells resulting in the fast reduction of the inflammation that may cause a heart attack, offering a new way to treat people at risk for heart disease.
“In just one week our novel cell proliferation-specific approach successfully suppressed atherosclerotic plaque growth and inflammation in mice engineered to mimic human vascular disease,” says lead study author Jun Tang, MS, a PhD student at Icahn School of Medicine at Mount Sinai.
“Atherosclerosis is a major cause of death around the globe, and our nanomedicine strategy promises to offer a new way to reduce the number of heart attacks and strokes.”
Building upon a recent discovery, that macrophage proliferation dictates atherosclerosis-related vessel wall inflammation, the research team applied a nanomedicine strategy with a molecule of “good cholesterol,” or high-density lipoprotein (HDL), a naturally occurring shuttle that travels from the liver to arteries. The team took advantage of HDL’s natural travel routes, loading it with the widely-used cholesterol-lowering medication called simvastatin (Zocor), which it shuttles into arterial walls.
The simvastatin-loaded nanoparticles, named S-HDL, work by targeting inflamed immune cells called macrophages within high-risk arterial plaques. These macrophages become laden with cholesterol and start proliferating in plaques, thereby increasing inflammation. This lipid-driven inflammatory process drives atherosclerotic plaque buildup and rupture leading to a heart attack or stroke.
Since patients hospitalized after heart attack or stroke have a high recurrence rate of up to 20 percent within three years, the researchers also tested the possible benefits of adding an eight-week regimen of oral statins after the one-week S-HDL nanotherapy. Mice study results showed superior long-term therapeutic benefits of a combined total nine-week S-HDL and oral statins regimen, by first rapidly reducing plaque inflammation and then continuously keeping it suppressed.
“We envision our S-HDL nanomedicine therapy could be translated quickly to human clinical trials as a short-term infusion therapy for heart attack and stroke patients to rapidly suppress plaque inflammation, which can be sustained using current standard of care oral statin medication,” says Zahi Fayad, PhD.
While more research is needed, the results thus far are exciting.
“Nanotherapeutically inhibiting local macrophage proliferation is possible and we can effectively apply it to treat inflammation inside arteries.”
“Collectively, our results demonstrate that the two-step regimen not only reduces macrophage accumulation but also reduces the expression of key genes linked to inflammation in this cell type,” says senior study author Willem Mulder, PhD.
Researchers look forward to translating their promising mice study findings to larger animal models and human clinical trials in the near future. While more research needs to be done (and realistically a lot of promising drugs and research really doesn’t pan out) this offers hope for many people, all around the world.
Jun Tang, Mark E. Lobatto, Laurien Hassing, Susanne van der Staay, Sarian M. van Rijs, Claudia Calcagno, Mounia S. Braza, Samantha Baxter, Francois Fay, Brenda L. Sanchez-Gaytan, Raphaël Duivenvoorden, Hendrik B. Sager, Yaritzy M. Astudillo, Wei Leong, Sarayu Ramachandran, Gert Storm, Carlos Pérez-Medina, Thomas Reiner, David P. Cormode, Gustav J. Strijkers, Erik S. G. Stroes, Filip K. Swirski, Matthias Nahrendorf, Edward A. Fisher, Zahi A. Fayad, & Willem J. M. Mulder (2015). Inhibiting macrophage proliferation suppresses atherosclerotic plaque inflammation Science Advances : 10.1126/sciadv.1400223
This entry was posted on April 3, 2015 by Dr. Jekyll. It was filed under Health and Medicine and was tagged with cardiology, cholesterol, health, internal medicine, medicine, metabolic diseases, metabolism, nanotechnology, peer reviewed, science, stroke.