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Enzyme controls ’good cholesterol’

27.02.2003

A recently discovered enzyme called endothelial lipase regulates the structure, metabolism and blood concentration of high density lipoprotein (HDL), the so-called "good cholesterol," said researchers from Baylor College of Medicine in a report in the online version of the Proceedings of the National Academy of Sciences.

In a series of studies in mice, Dr. Lawrence Chan, chief of the section of endocrinology and metabolism at Baylor, his co-workers and colleagues from the section of cardiology and atherosclerosis have found that when mice lack this enzyme, the particles of HDL in their blood are much larger than normal.

"We don’t know if it is good or bad that the HDL becomes larger," said Chan. "We were always taught that high levels of HDL are good for you because HDL carries cholesterol from the outer areas of the body back to the liver where it is excreted as bile."

High levels of HDL may also inhibit inflammation, a newly accepted factor in coronary heart disease, Chan said.

"It also protects the vascular wall," he said. "It may also slow down the oxidation of low density lipoprotein (the so-called bad cholesterol). Oxidized LDL is very bad."

A variant of the enzyme that is found in approximately 26 percent of people is associated with high levels of HDL, he said. He and his colleagues are studying the fate of patients with this type of enzyme to determine whether it is beneficial or not.

Once they determine whether the variant form of HDL is good or bad, it can become a target for drug developers who will attempt to manipulate levels of "good" cholesterol through this mechanism.

One concern is that the larger particles of HDL might slow the transport of cholesterol back to the liver, which probably would not be good, said Chan. While HDL might have all the good actions including working against inflammation and protecting the vascular wall, that would have to be balanced against the interruption of cholesterol transport to the liver.

In his experiments, he found that metabolism of HDL is a lot slower without the enzyme.

"That’s why the concentration goes up as the HDL accumulates," he said.

Others who participated in the study included Drs. Ke Ma, Mehmet Cilingiroglu, Christie M. Ballantyne and Ali J. Marian, all of Baylor, and Dr. James Otvos of LipoScience of Raleigh, NC.