Low-density lipoprotein (LDL) is the so-called “bad cholesterol” often linked to medical problems like heart disease and clogged arteries. Cells in the liver produce a specific receptor that sticks to LDL and removes it from the blood, lowering cholesterol levels. Statin drugs also reduce LDL cholesterol levels by boosting cells’ production of the receptor.
Using a mouse model, UCLA scientists discovered a new mechanism that controls cells’ production of LDL receptor. The team identified an enzyme called Idol that destroys the receptor, permitting more LDL cholesterol to circulate in the blood. In blocking Idol’s activity, the researchers triggered cells to make more receptor and absorb more cholesterol from the body.
“We only know of three pathways that regulate the LDL receptor. The first two are already targeted by existing drugs,” explained Dr. Peter Tontonoz, professor of pathology and laboratory medicine at the David Geffen School of Medicine at UCLA and an investigator at the Howard Hughes Medical Institute. “Idol is the first mechanism discovered in several years that may lead to a new medication designed to control cholesterol levels.”
The findings suggest that development of a drug that interferes with Idol’s activity could influence cholesterol metabolism and lower levels of bad cholesterol. Doctors could prescribe the new medication in conjunction with statin drugs, which also cut cholesterol levels by targeting a different enzyme linked to the LDL receptor. This could benefit patients that cannot tolerate statin-related side effects.
Tontonoz collaborated with Noam Zelcer, Cynthia Hong and Rima Boyadjian. The research was funded by the Howard Hughes Medical Institute and the National Heart, Lung and Blood Institute. Tontonoz and Zelcer have filed a patent related to the research findings.
The research appears in the June 11 online edition of the journal Science.
Image showing how the LDL receptor changes appearance after contact with the Idol enzyme.