Recent findings by researchers affiliated with Brown’s Giuliani RNA Center could inform new treatments for heart disease. 

The study, which was published in Nature Cardiovascular Research, showed that removing a protein called AIMP3 from heart cells in mice led to severe heart problems, including inflammation, scarring, and fatal heart failure. 

“AIMP3 is a protein that had never been studied in the heart and was of unclear function,” says senior author Federica Accornero, PhD, the George D. Eggleston Professor of Biochemistry. “What we discovered is that cardiac AIMP3 is crucial for survival.” 

AIMP3 is part of a larger cellular machinery responsible for building other proteins. The precise functions of the proteins are unknown, but scientists thought that AIMP3 affects how much protein the heart makes, Accornero says. Instead, they discovered that AIMP3 is essential to avoiding mistakes in protein synthesis. The finding could have an impact even beyond the heart, she adds, because AIMP3 may exert the same function in cells in other organs.

The research team, led by Anindhya S. Das, PhD, an American Heart Association Postdoctoral Fellow in Accornero’s lab, used gene editing techniques to knock out AIMP3 in mice and then observed the effects. They found that the key role of AIMP3 is to help another protein, MetRS, remove a harmful substance called homocysteine. Without AIMP3, homocysteine builds up in heart cells, causing damage by inducing oxidative stress, protein aggregation, and defective mitochondria, leading to cell death. When the researchers removed AIMP3 from heart muscle cells in mice, the mice developed severe heart problems and eventually died. 

“Overall, we uncovered a unique role of AIMP3 in maintaining the editing activity of MetRS and its essential role in heart function and survival,” Das says. 

He adds that understanding the mechanism could lead to new treatments for heart diseases linked to homocysteine buildup. The team next plans to determine how they might use the discovery to develop preventive treatments for heart disease.