Can the bad cholesterol enzyme be 'turned off'?

Scientists at the University of Texas at Arlington (USA) have identified a new enzyme that can be deactivated to help the body maintain healthy cholesterol levels. This finding , if confirmed, would be a significant breakthrough that could lead to new treatments for diseases that affect millions of people worldwide: data from the World Heart Federation indicates that some 4.4 million people died in 2019 from high cholesterol.

"We found that by blocking the enzyme IDO1, we can control inflammation in macrophages, a type of immune cell," said Subhrangsu S. Mandal, senior author of the new study and a professor of chemistry at The University of Texas at Arlington.

"Inflammation is linked to many conditions, from heart disease to cancer, diabetes, and dementia . By better understanding IDO1 and how to block it, we have the potential to better control inflammation and restore proper cholesterol processing, thereby halting many of these diseases," he explained.

Inflammation plays a crucial role in the immune system , helping the body both fight infections and heal injuries. However, when inflammation becomes abnormal—due to stress, injury, or infection—it can damage cells, disrupt their normal function, and increase the risk of serious illness. During these periods, macrophages cannot absorb cholesterol properly, which can lead to chronic disease.

The team that published the discovery discovered that the enzyme IDO1 is activated during inflammation, producing—particularly in the liver—a substance called kynurenine , which interferes with the processing of cholesterol by macrophages.

However, when IDO1 is blocked, macrophages regain their ability to absorb cholesterol. This suggests that reducing IDO1 activity could offer a new avenue for preventing heart disease by keeping cholesterol levels in check.

Second finding

The researchers also found that nitric oxide synthase (NOS)—another enzyme linked to inflammation—worsens the effects of IDO1: they believe inhibiting this enzyme could offer another potential treatment for controlling cholesterol problems caused by inflammation.

“These findings are important because we know that excessive cholesterol accumulation in macrophages can lead to clogged arteries, heart disease, and many other conditions,” Mandal said. “Understanding how to prevent the inflammation that affects cholesterol regulation could lead to new treatments for conditions such as heart disease, diabetes, cancer, and others.”

The Texas university's research team's next steps will focus on further investigating how IDO1 interacts with cholesterol regulation and whether other enzymes play a role. If they can find a safe way to block IDO1, it could pave the way for more effective drugs to prevent inflammation-related diseases.