Putrescine,
the compound responsible for perhaps the foulest odor in nature -- the smell of
decomposing flesh -- may also be a remedy for atherosclerosis and other chronic
inflammatory diseases, according to a new study led by researchers at Columbia
University Irving Medical Center.
This
unusual discovery stems from an investigation into the body's process for
removing dead cells using macrophages, a type of white blood cell that digests
dead cells.
Normally,
the process is initiated within minutes of cell death. However, studies have
suggested that this essential housekeeping task is impaired in atherosclerosis,
promoting the accumulation of plaques.
To
learn more, Tabas, Arif Yurdagul Jr, PhD, associate research scientist in the
Tabas lab, and colleagues set up human
macrophages and dying cells in a dish and watched how the process unfolded.
That's
when they detected the role of putrescine. Macrophages, they found, reclaim
arginine and other amino acids from the dead cells they engulf and use an
enzyme to convert arginine into putrescine. Putrescine then activates a protein
(Rac1) that signals the macrophages to eat more dead cells.
The
results suggested atherosclerosis may be partly a putrescine problem, so the
researchers turned to mice with atherosclerosis to investigate.
The
researchers found that mice with worsening atherosclerosis had a short supply
of putrescine because they didn't have enough of a key enzyme (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."
The
findings suggest that putrescine could be used to treat atherosclerosis and
other conditions characterized by chronic inflammation, such as Alzheimer's.
"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 Tabas, whose findings
were published online Jan. 30 in the journal Cell Metabolism.
"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."
See:
Posted by Dr. Tim Sandle, Pharmaceutical Microbiology Resources (http://www.pharmamicroresources.com/)
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