New enzyme can be "turned off" to restore cholesterol balance and reduce inflammation

Scientists at The University of Texas at Arlington have identified a new enzyme that can be "turned off" to help the body maintain healthy cholesterol levels-a significant development that could lead to new treatments for diseases that affect millions of Americans.

We found that by blocking the enzyme IDO1, we are able to control the inflammation in immune cells called macrophages. Inflammation is linked to so many conditions-everything from heart disease to cancer to diabetes to dementia. By better understanding IDO1 and how to block it, we have the potential to better control inflammation and restore proper cholesterol processing, stopping many of these diseases in their tracks."

Subhrangsu S. Mandal, lead author of a new peer-reviewed study and professor of chemistry at UT Arlington

Inflammation plays a crucial role in the immune system, helping the body fight infections and heal injuries. But when inflammation becomes abnormal-due to stress, injury or infection-it can damage cells, disrupt normal functions and increase the risk of serious diseases. During these periods, macrophages can't absorb cholesterol properly, which can lead to chronic disease.

The team-Dr. Mandal, postdoctoral researcher Avisankar Chini; doctoral students Prarthana Guha, Ashcharya Rishi and Nagashree Bhat; master's student Angel Covarrubias; and undergraduate researchers Valeria Martinez, Lucine Devejian and Bao Nhi Nguyen-found that the enzyme IDO1 becomes activated during inflammation, producing a substance called kynurenine that interferes with how macrophages process cholesterol.

When IDO1 is blocked, however, macrophages regain their ability to absorb cholesterol. This suggests that reducing IDO1 activity could offer a new way to help prevent heart disease by keeping cholesterol levels in check.

The researchers also found that nitric oxide synthase (NOS), another enzyme linked in inflammation, worsens the effects of IDO1. They believe that inhibiting NOS could provide another potential therapy for managing cholesterol problems driven by inflammation.

"These findings are important because we know too much cholesterol buildup in macrophages can lead to clogged arteries, heart disease and a host of other illnesses," Mandal said. "Understanding how to prevent the inflammation affecting cholesterol regulation could lead to new treatments for conditions like heart disease, diabetes, cancer and others."

Next, the research team plans to dig deeper into 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 open the door for more effective drugs to prevent inflammation-related diseases.