Arlington Enzyme Breakthrough: IDO1 Discovery Could Revolutionize Heart Health
A groundbreaking discovery by researchers at The University of Texas at Arlington (UTA) has unveiled a new enzyme, IDO1, that could transform cholesterol management and offer hope for millions battling heart disease. Published on May 1, 2025, in the journal Langmuir, the study reveals that blocking IDO1 can control inflammation in immune cells called macrophages, restoring their ability to process cholesterol effectively. This Arlington enzyme breakthrough, led by Professor Subhrangsu S. Mandal, may pave the way for innovative treatments for heart disease, diabetes, cancer, and other inflammation-related conditions affecting over 125 million Americans.
Unveiling the Role of IDO1
The research team, including 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, discovered that IDO1 becomes active during inflammation. This activation produces kynurenine, a molecule that disrupts cholesterol uptake in macrophages, leading to cholesterol buildup and the formation of foam cells, a hallmark of atherosclerosis. By blocking IDO1, the team restored macrophages’ cholesterol-processing capabilities, potentially preventing clogged arteries and reducing the risk of heart disease.
“We found that by blocking the enzyme IDO1, we can control inflammation in immune cells called macrophages,” said Mandal. “Inflammation is linked to so many conditions—from heart disease to cancer, diabetes, and dementia. By better understanding IDO1 and how to block it, we have the potential to stop many of these diseases in their tracks.” The study also identified nitric oxide synthase (NOS) as an enzyme that amplifies IDO1’s effects, suggesting that targeting both could enhance therapeutic outcomes.
Why This Matters
Cholesterol dysregulation is a major driver of cardiovascular disease, which remains the leading cause of death in the United States, claiming over 600,000 lives annually. Macrophages, the body’s immune system “janitors,” normally absorb excess cholesterol to prevent arterial plaque buildup. However, during chronic inflammation—triggered by stress, injury, or infection—IDO1 produces kynurenine, which impairs this process. The resulting cholesterol accumulation in macrophages contributes to atherosclerosis, diabetes, and other metabolic disorders. Blocking IDO1 could restore cholesterol homeostasis, offering a novel approach to preventing these conditions.
The study’s findings build on prior research showing that inflammation disrupts cholesterol metabolism through pathways like NF-κB signaling and molecules such as lipopolysaccharides (LPS) and interferon-gamma (IFNγ). By targeting IDO1, researchers aim to interrupt this cycle, potentially reducing the risk of foam cell formation and subsequent heart disease. The discovery of NOS’s role further expands the therapeutic potential, as dual inhibition could address a broader range of inflammation-driven cholesterol issues.
Arlington’s Role in Medical Innovation
Conducted at UTA, a tier-one research institution with $155 million in research expenditures in 2024, this study underscores Arlington’s growing prominence in medical innovation. The university’s Department of Chemistry and Biochemistry, supported by grants from the National Institutes of Health (1 R15 997 HL170257-01), the National Science Foundation (NSF AGEP 998 Award – 2243017), and the Schwartzberg Companies, has positioned itself at the forefront of biomedical research. This Arlington enzyme breakthrough adds to UTA’s legacy of advancing health solutions, following recent studies on heart testing methods and gene research accuracy…