Heart Disease Clue Uncovered
Reported February 4, 2010
(Ivanhoe Newswire) -- When it comes to the
development of atherosclerosis and heart disease, it's not about any one bad
actor -- it's about a whole network gone wrong.
New study findings highlight a pretty remarkable
thing, study author Jay W. Heinecke, of the University of Washington, Seattle,
was quoted as saying. "Despite 30 years of study, we still don't know how
cholesterol causes heart disease," Heinecke said. With the new findings,
scientists are getting closer.
Scientists know that heart disease is about more
than just high LDL ("bad") cholesterol. Cells known as macrophages also play a
critical role. Macrophages are part of the immune system and work to gobble up
pathogens and clear away dead cells. But they also take up and degrade
cholesterol derivatives. When they get overloaded with lipoproteins, they take
on a foamy appearance and become what scientists refer to as foam cells. Those
foam cells are the ones that seem to have critical importance in the development
Heinecke explained that macrophages end up with
too much cholesterol going in and not enough coming out. The macrophages get
overwhelmed and trapped in the artery wall, and plaques form as a result. There
is an integrated network of macrophage proteins involved. When that network gets
disrupted, as it does when too much cholesterol comes in, atherosclerosis forms.
"It's definitely a different way to think about
what is going on," Heinecke said.
Heinecke's group applied technologies and
statistical tools to get a global view of what happens to macrophage proteins
when they turn into foam cells. Their analysis revealed what they call a
macrophage sterol-responsive network (MSRN) that includes proteins already known
to work together.
The researchers found that drugs used to lower
cholesterol and inflammation restore the macrophage network to almost normal,
even in mice that don't have the LDL receptors that are considered the usual
targets of the drugs. On the other hand, mice lacking single proteins in the
network have macrophages that look like foam cells even when they aren't loaded
Thus, anything that sends the macrophage network
off kilter could promote heart disease, said Heinecke. These findings may change
the way researchers think about how heart disease is treated. The key may be how
to best restore the function of an integrated network rather than to lower
cholesterol levels or ratchet individual proteins up or down.
"We propose that the atherogenic actions of
cholesterol-loaded macrophages are an emergent property that results when the
normal balance of MSRN proteins in microvesicles is perturbed," researchers
wrote. "We further suggest that certain dietary factors or genetic variations
can disturb this network, thereby promoting vascular disease. By integrating
mouse and human data, we hope to better understand the MSRN's role in foam cell
formation, with the long-term goal of identifying therapeutic interventions for
targeting networks rather than individual proteins."
SOURCE: Cell Metabolism, February 3, 2010