The cholesterol conundrum  pg. 3

Fibrates, another class of drug already on the market that potentially can raise HDL levels, are usually used in tandem with statins to treat high cholesterol. But they can cause potentially serious side effects, including kidney damage.

A few years ago, researchers showed that infusions of a synthetic form of HDL, called “ApoA1 Milano,” could significantly reduce atherosclerotic lesions as detected by intravascular ultrasound. But the need to inject it by vein every week makes this option impractical for widespread use.

For several years, Fazio and Linton have studied a protein that binds fatty acids in both macrophages and fat cells. As such, the adipocyte fatty acid binding protein (aP2) plays a crucial role in inflammation and insulin resistance, factors driving both diabetes and atherosclerosis.

“It turns out that in addition to cholesterol, fatty acids play critical roles in promoting both plaque build-up in the arteries and the development of adult onset diabetes,” Linton explains. “Coronary heart disease is the most common cause of death in diabetes,” he says, “and we believe that aP2 is a critical link between these disease processes.”

In a recent article published in the journal Nature, the Vanderbilt researchers and their colleagues at the Harvard School of Public Health and Bristol-Myers Squibb reported that an aP2 inhibitor prevented the development of atherosclerosis and diabetes in mice.

“These studies are tremendously exciting,” says Linton, “because they support the potential development of a single therapeutic approach for the treatment of diabetes and the prevention of coronary heart disease.”

Endothelium that is injured, in this case by high levels of low-density lipoprotein (LDL) cholesterol, releases factors that attract blood cells called monocytes.  Once inside the tissue, the monocytes differentiate into macrophages.  Part of their job is to sweep up excess cholesterol.  As they become engorged with cholesterol, the macrophages take on a foamy appearance, and now are called foam cells.

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