Cholesterol’s link to heart disease gets clearer - and more complicated
By considering molecular level events on a broader scale, researchers now have a clearer, if more complicated, picture of how one class of immune cells goes wrong when loaded with cholesterol. The findings reported in the February 3rd issue of Cell Metabolism, a Cell Press publication, show that, when it comes to the development of atherosclerosis and heart disease, it’s not about any one bad actor - it’s about a network gone awry.

The new findings also highlight a pretty remarkable thing, Heinecke says: “Despite 30 years of study, we still don’t know how cholesterol causes heart disease.” But, with the new findings, scientists are getting closer.

Earlier studies had shown 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 innate immune system that typically gobble up pathogens and clear away dead cells. But they also take up and degrade cholesterol derivatives. When they get overloaded with those lipoproteins, they take on a foamy appearance under the microscope to become what scientists aptly refer to as foam cells. Those foam cells are the ones that seem to have critical importance in the development of atherosclerosis.

People had typically thought about this problem in terms of linear pathways, Heinecke explained. In essence, 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 somehow plaques form as a result.

But the new results show that it isn’t really about simple paths in and out; rather, 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 says.

Heinecke’s group applied sophisticated 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), including proteins already known to work together. Most of them are also found in one place, within microvesicles outside the macrophage cells.

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Thanks to powerful cholesterol-lowering statin drugs, driving down low-density lipoprotein (LDL), or “bad” cholesterol, has been the primary approach to improving cholesterol levels. But there’s more to the story of cholesterol and cardiovascular risk than LDL alone. Another key player is high-density lipoprotein (HDL), the “good” cholesterol. Higher levels of HDL are associated with lower cardiovascular risk. The good news about this good cholesterol is that simple lifestyle changes can help boost HDL, reports the June 2008 issue of Harvard Women’s Health Watch.

HDL removes LDL from artery walls and ferries it to the liver for processing or removal. HDL also fights potentially dangerous inflammation and clot formation. According to a recent review of research on HDL, there’s some evidence that increasing HDL can reduce the risk of heart attack and stroke even without changes in LDL.

Harvard Women’s Health Watch suggests several things people can do to nudge up HDL levels. Most of these strategies also improve health in other ways.

1. Get aerobic exercise. Moderate to vigorous aerobic exercise can boost HDL by 5% to 10%. Aim for five 30-minute sessions per week.

2. Lose weight if you need to. If you’re overweight or obese, you can boost your HDL level by about 1 mg/dL for every seven pounds lost, although any amount of weight loss will help.

3. If you smoke, quit. HDL levels rise by as much as 15% to 20% after you quit.

4. Eat a healthy diet. Avoid trans fats, which increase bad cholesterol and decrease good cholesterol. Avoid highly refined carbohydrates, such as white-flour products.

5. Consider medications. Niacin, available over the counter, is the most effective HDL-raising medication available. Niacin can be strong medicine work with your clinician if you want to try it.

Source: www.health.harvard.edu