Researchers at UT Southwestern found a liver protein that acts like a switch for cholesterol. The protein, called HELZ2, helps control how many cholesterol‑carrying particles leave the liver and enter the blood.
HELZ2 works by making the messenger that tells cells to build a protein called apoB disappear faster. Less apoB means the liver makes fewer lipoproteins, the tiny bubbles that move cholesterol and fat around the body.
How HELZ2 Lowers Bad Cholesterol
When HELZ2 is more active, the messenger RNA for APOB breaks down quickly. The result is fewer apoB proteins and fewer low‑density lipoprotein (LDL) particles, the type of cholesterol linked to heart attacks.
What Happens in Mice
Scientists gave mice a mutation that boosts HELZ2. Those mice had lower LDL and lower triglycerides in their blood and were protected from artery clogging. However, they also stored more fat in their livers.
Normal mice without the mutation showed the opposite: higher blood cholesterol but less liver fat. This shows a trade‑off between blood cholesterol and liver fat.
"HELZ2 works like a dial between the liver and the bloodstream. Turn it up, and blood cholesterol drops while liver fat rises. Turn it down, and the opposite happens," said Dr. Zhang.
A New Way to Fight Heart Disease
Most patients use statins, drugs that block cholesterol after it is made. HELZ2 offers a different approach: it stops cholesterol before the protein is even created. By fine‑tuning HELZ2, doctors might lower dangerous cholesterol and also help people with fatty liver disease.
"Controlling apoB at the RNA level is a big change in how we think about cholesterol," Dr. Zhang added. "It gives us a new molecular lever for treatment."