Inflammation-reducing molecule provides a new target for treating atherosclerosis

Researchers at Case Western Reserve University have identified a new target to treat atherosclerosis, a condition where plaque clogs arteries and causes major cardiac issues, including stroke and heart attack.

In a new study, published in the journal Cell Reports, the team identified an inflammation-reducing molecule—called itaconate (ITA)—that could be the foundation of a new approach to treat such a common and deadly disease.

Heart disease is the leading cause of death for men, women and people of most racial and ethnic groups, according to the U.S. Centers for Disease Control and Prevention.

Medications help but don’t completely protect patients from cardiovascular risk. So, doctors also recommend lifestyle changes, such as a low-cholesterol/low-fat diet (LCLFD), to further reduce plaque and inflammation that increase the risk of cardiovascular disease. Yet many patients find it challenging to follow diet restrictions long-term.

Identifying the role ITA plays in diet and heart disease may help address this.

“We’ve found that itaconate is crucial to the diet’s ability to stabilize plaques and reduce inflammation, which has been a mystery until now,” said Andrei Maiseyeu, associate professor at the Cardiovascular Research Institute and Department of Biomedical Engineering at Case Western Reserve’s School of Medicine.

“This discovery marks a major leap forward in the understanding of how diet-induced plaque resolution occurs at a molecular level.”

Based on their discovery, Maiseyeu and his team have developed a new treatment: ITA-conjugated lipid nanoparticles. This new therapeutic approach allows ITA to accumulate in plaque and bone marrow, where it reduces inflammation and mimics the beneficial effects of LCLFD without requiring drastic lifestyle changes.

“We have already seen its effectiveness in multiple models of atherosclerosis,” Maiseyeu said. “We are optimistic that this will result in better treatments that will greatly lower the long-term risk of heart attacks and strokes while also improving patients’ quality of life.”

Maiseyeu and his team are now taking steps to translate ITA-LNP to the clinic, including engineering a pill form of the treatment, which they believe will not only be convenient for patients, but also transformative.

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