Possible Unexpected Atherosclerosis Treatment

"It's estimated that a billion cells die in the body every day, and if you don't get rid of them, they can cause inflammation and tissue death," says Ira Tabas, MD, Ph.D., the Richard J. Stock Professor of Medicine and professor of pathology & cell biology (in physiology & cellular biophysics) at Columbia University Vagelos College of Physicians and Surgeons. "Removing these dead cells by a process called 'efferocytosis' (from the Latin 'to carry to the grave') is one of the body's most important functions."

Typically the efferocytosis process is initiated within moments of cell death, but studies suggest that this task becomes impaired with atherosclerosis which promotes the accumulation of plaques. To investigate the process further the researchers set up human macrophages and dying cells in a dish to observe how this process unfolds; this is when the role of putrescine was revealed, according to the researchers macrophages reclaim arginine and other amino acids from engulfed dead cells and use an enzyme to convert arginine into putrescine, which then activates Pac1 proteins that signal macrophages to eat more dead cells.

Findings suggest that atherosclerosis may be partly related to putrescine, to investigate the researchers selected mice with the condition. Mice with worsening atherosclerosis were found to have shortened supplies of putrescine because they were lacking in enough arginase-1 to make the compound. 

"But when we put putrescine in the animals' drinking water, their macrophages got better at eating dead cells and the plaques improved. Fortunately, when you dissolve putrescine into water, at least at the dosages needed to improve the plaques, it no longer gives off its odor. The mice drank it without any problem and show no signs of sickness," says Ira Tabas, MD, Ph.D.

“Of course we do not yet know the feasibility and safety of using low-dose putrescine to ward off atherosclerotic heart disease and other diseases driven by defective efferocytosis. However, the study shows the potential of treating heart disease with compounds that help macrophages eat dead cells and that are currently in clinical trials for other indications."