Cholesterol-lowering drugs known as statins are at the forefront of the fight against heart disease. They work by blocking the synthesis of cholesterol inside cells. This, in turn, causes cells to produce more of a compound known as low-density-lipoprotein receptor, or LDLr, which plucks dangerous cholesterol from the bloodstream.
Despite the success of statins, they don’t work for everyone. Now, a team of researchers with GlaxoSmithKline in Les Ulis, France, has found another way of reducing cholesterol. Working with cell cultures, the researchers began by genetically engineering human cells to express a fluorescent protein when the DNA that normally activates the LDLr gene is active. Then, they searched for compounds that increased the cells’ fluorescence. Such chemicals, they reasoned, would boost LDLr activity in normal cells.
After spotting a likely compound, the researchers added it to normal cell cultures and found that the cells indeed took up more cholesterol than normal.
In hamsters fed both normal and high-fat diets, the agent reduced blood concentrations of low-density-lipoprotein (LDL) cholesterol and fatty acids by as much as 80 percent. The researchers report their findings in the December 2001 Nature Medicine.
Unlike statins, these new compounds continue to work even when cells are stuffed with LDL, so they could be more effective at reducing cholesterol, says Daniel J. Rader of the University of Pennsylvania School of Medicine in Philadelphia. However, he cautions, this may also disrupt normal cellular breakdown of fats, which could cause side effects.