Specially formulated ultra-tiny particles could curtail the growth of fat-laden deposits in blood vessels that can produce heart attacks and strokes, according to research from two groups of scientists in the U.S.
Cardiovascular disease is a leading cause of ill-health and death worldwide. High levels of cholesterol in the blood along with chronic inflammation in arterial walls lead to ‘plaques’ of fatty deposits getting established in blood vessels and growing in size.
Should one of the plaques break open, blood clots can form that block the artery. If a coronary artery gets blocked as a result, a heart attack ensues. A stroke is produced when a blood vessel supplying the brain is affected.
Despite the success of cholesterol-lowering statins, the burden of cardiovascular disease in developed countries had remained immense, noted Oliver Soehnlein of the Institute for Cardiovascular Prevention at Munich in Germany.
Consequently, much research over the past 20 years had focused on development of anti-inflammatory strategies. However, many of these efforts had been unsuccessful at the preclinical or clinical stages, and “new therapeutic approaches are sorely needed,” he said in a commentary that accompanied a paper just published in Science Translational Medicine .
In that paper, scientists at Columbia and Harvard universities described trials carried out in mice with biodegradable nanoparticles. These nanoparticles were targeted at plaques with incorporation of a molecule that would bind to a substance found at such sites, type IV collagen.
In addition, the nanoparticles slowly released another compound, Ac2-26, that latched on to a protein, N -formyl peptide receptor 2 (FPR2/ALX), carried by immune cells — monocytes and macrophages — that drive inflammation in the plaques.
The nanoparticles were tested in laboratory mice with a genetic predisposition for high cholesterol in their blood that were fed a Western diet. The mice that received injections of the nanoparticles had much less plaque formation in advanced stages, reported Gabrielle Fredman and the other scientists in their paper.
The binding of Ac2-26 to the FPR2/ALX receptor had led to a dampening of excessive inflammation, without compromising normal immune function, and also initiated healing of damage to the arterial wall that occurred during plaque formation.
In another paper published this week in Proceedings of the National Academy of Sciences (PNAS) , Prabhas Moghe of Rutgers University and colleagues spoke of developing nanoparticles with molecules that were specifically designed to strongly bind a receptor on macrophages. The receptor was involved in the uptake of fats into these immune cells, which then stimulated the inflammatory process.
Mice treated with the nanoparticles developed less pronounced plaques.
The nanoparticles described in the Science Translational Medicine paper could become a “significant approach” for treating cardiovascular disease, assuming that what had been shown with mice also held true in humans, observed C.C. Kartha, a professor at the Rajiv Gandhi Centre for Biotechnology in Thiruvananthapuram who studies the development of heart disease.
Mice that got the nanoparticles grew a thicker protective layer (or cap) over their plaques. As a result, such plaques were less likely to rupture. “At present, there are no drugs that can stabilise plaques and increase their cap thickness,” he pointed out.
