New data on the pathogenesis of atherosclerosis

Ideas about the growth of atherosclerotic plaques will have to be revised

NanoNewsNet based on University of Toronto materials: New study redefines how plaques grow in heart diseaseThe growth of deadly plaques in the walls of the arteries may not occur at all as scientists have so far believed.

This conclusion is summed up by the data obtained during a study conducted by specialists from the University of Toronto (University of Toronto) and Massachusetts General Hospital (Massachusetts General Hospital). The results of this work offer pharmaceutical companies a new potential therapeutic target for the treatment of atherosclerosis, one of the leading causes of cardiovascular diseases and mortality worldwide.

Scientists have found that atherosclerosis-causing white blood cells macrophages replicate inside plaques. Moreover, this growth does not depend on cells outside the plaques – monocytes – as previously assumed (see Fig.).

"Until now, it was believed that inflammatory macrophages are formed mainly as a result of attracting their precursors, monocytes, from the blood," explains the study's lead author Clint Robbins, associate professor of laboratory Medicine and Pathobiology and Immunology at the University of Toronto. "Our study shows that the accumulation of macrophages also depends on their local proliferation in the developing plaque."

The significance of this study for the clinic may be very significant. Many pharmaceutical companies are investing in the development of drugs that can block the attraction of white blood cells to plaques. But if macrophages independently maintain their population in the plaque by local division, blocking the attraction of monocytes from the blood is far from the best strategy.

"I think this work will force a lot of serious rethinking," says study leader Filip Swirski, a researcher at the Center for Systems Biology at Massachusetts General Hospital and an associate professor at Harvard Medical School. "So far, the target in the treatment of atherosclerosis has been the influx of monocytes, but as an additional or alternative approach, the proliferation of macrophages should also be taken into account, especially in severe pathology."

This approach is probably more justified than targeting circulating monocytes, since interrupting pathological processes directly in the plaques will preserve other beneficial immune reactions under the control of monocytes, the scientist believes.

In addition, it can help improve the current standard of medical care in the treatment of atherosclerosis – statin therapy. Statins, in addition to lowering the level of plaque-promoting lipids in the blood, have anti-inflammatory properties. Researchers are now investigating whether statins can limit the proliferation of macrophages in plaques.

According to Dr. Robbins, additional targeting of macrophage proliferation can further reduce inflammation and prove to be clinically effective.

The experiments were conducted on mice, and scientists warn that additional large-scale studies are needed to confirm their results in relation to the human body. However, evidence of macrophage growth in plaques in human carotid arteries has already been found.

In the near future, scientists plan to compare the proliferation of macrophages and participation in the development of atherosclerosis of monocytes at different stages of the disease, as well as to find out whether all macrophages, or only some of their subpopulations, exhibit the ability to replicate in plaques.

Article by Robbins et al. Local proliferation dominates lesional macrophage accumulation in atherosclerosis published in the journal Nature Medicine.

Portal "Eternal youth" http://vechnayamolodost.ru14.08.2013