LDL receptor reduces LDL production, removes cholesterol from blood

poB is degraded inside the cells before they secrete very low-density lipoprotein into the blood.

Attie led the research team, which included Jaap Twisk, Donald Gillian-Daniel, Angie Tebon, Lin Wang, and Hugh Barrett. Barrett is with the University of Western Australia in Perth; the others were with the UW-Madison at the time the research was done. Twisk is now with the University of Leiden in the Netherlands, and Wang is at the University of California-San Diego in La Jolla, Calif.

The scientists studied liver cells from mice with functional LDL receptors and mice with mutant, nonfunctional receptors. Mice with the mutation showed symptoms analogous to those of people with FH. Their average blood cholesterol level was more than three times that of mice with functioning receptors.

The researchers examined how the presence or absence of LDL receptors affected the secretion of apoB from mouse liver cells. They studied apoB secretion from cells with receptors, from cells with the mutation, and from mutant cells they altered by introducing unusually large numbers of functional receptors.

"We found that although all three types of cells synthesized the same amount of apoB, they degraded different amounts before secreting it," Attie says.

The study found that liver cells with functional receptors degraded 55 percent of the apoB they made before releasing it. Liver cells with FH-like mutant receptors degraded only 20 percent of the apoB they made. However, when large numbers of functional receptors were added to those same mutant cells, they degraded 90 percent of the apoB they synthesized before secreting it.

The results also explain why statin medications -- which include the brands Lipitor, Zocor, Pravachol, Lescol, Mevacor and Baycol -- are effective in lowering serum LDL levels. As a class of pharmaceuticals, statins inhibit cholesterol production. Liver cells respond to this decrease in cholesterol by producing more LDL receptors on their surf

Contact: Alan Attie
University of Wisconsin-Madison

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