Heart Disease Clue Uncovered

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 of atherosclerosis.


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 with cholesterol.


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