Targeting the Enzyme Responsible for High Cholesterol Opens New Avenues for Inflammatory Disease Treatment

Researchers at The University of Texas at Arlington have identified a novel enzyme that can be inhibited to help maintain healthy cholesterol levels, signaling a breakthrough in potential therapies for various inflammatory diseases. The enzyme, known as IDO1, becomes activated during inflammation, producing kynurenine, which hampers macrophages’ ability to process cholesterol effectively. During periods of inflammation caused by stress, injury, or infection, this disruption can lead to damage to cells, impaired immune function, and increased risk for diseases such as heart disease, cancer, diabetes, and dementia.

The study, published in the journal Langmuir, demonstrated that blocking IDO1 restores macrophages' capacity to absorb cholesterol, thus preventing the accumulation that contributes to clogged arteries and cardiovascular issues. Additionally, the research uncovered that nitric oxide synthase (NOS), another enzyme involved in inflammation, exacerbates the effects of IDO1, suggesting that inhibiting NOS may offer further therapeutic benefits.

Lead researcher Subhrangsu S. Mandal explained that inflammation influences cholesterol regulation and that controlling this pathway could provide new strategies to combat chronic diseases. The team’s findings also suggest that targeting these enzymes could help prevent the development of inflammation-related conditions, including heart disease. Future investigations aim to explore the detailed interactions between IDO1 and cholesterol metabolism and to develop safe methods for enzyme inhibition, paving the way for innovative treatments.

This groundbreaking research highlights the potential of enzyme inhibition in managing inflammation-driven cholesterol dysregulation, offering hope for new drugs to prevent cardiovascular and other chronic diseases linked to inflammation.

Source: https://medicalxpress.com/news/2025-06-enzyme-high-cholesterol-pave-path.html