New findings by a crew of molecular biologists at Brown College on the essential function of a protein referred to as AIMP3 in coronary heart perform may inform new therapies for coronary heart illness.
In a research revealed in Nature Cardiovascular Analysis, the researchers confirmed that eradicating AIMP3 from coronary heart cells in mice led to extreme coronary heart issues, together with irritation, scarring and deadly coronary heart failure.
“AIMP3 is a protein that had by no means been studied within the coronary heart and was of unclear perform,” mentioned research writer Federica Accornero, an affiliate professor of biochemistry at Brown who’s affiliated with the College’s RNA Middle. “What we found is that cardiac AIMP3 is essential for survival.”
AIMP3 is an element of a bigger mobile equipment chargeable for constructing different proteins. The exact features of the proteins are unknown, however scientists suspected that AIMP3 impacts how a lot protein the center makes, Accornero mentioned. As a substitute, the researchers found that AIMP3 is crucial to avoiding errors in protein synthesis. The discovering may have an effect even past the center, she mentioned, as a result of AIMP3 may exert the identical perform in cells in different organs, as properly.
Within the mission led by Anindhya S. Das, a postdoctoral analysis affiliate in molecular biology, cell biology and biochemistry, the Brown analysis crew used gene enhancing methods to “knock out” AIMP3 in mice after which noticed the consequences.
They discovered that the important thing function of AIMP3 is to assist one other protein, MetRS, correctly “edit” or take away a dangerous substance referred to as homocysteine. With out AIMP3, homocysteine builds up in coronary heart cells, inflicting injury by inducing oxidative stress, protein aggregation and faulty mitochondria, resulting in cell demise. When the researchers eliminated AIMP3 from coronary heart muscle cells in mice, the mice developed extreme coronary heart issues and ultimately died.
“General, we uncovered a singular function of AIMP3 in sustaining the enhancing exercise of MetRS and its important function in coronary heart perform and survival,” Das mentioned.
These findings are important, Das added, as a result of they spotlight a brand new and important method AIMP3 protects the center, and understanding the mechanism may result in new therapies for coronary heart ailments linked to homocysteine buildup. As subsequent steps, the crew is conducting research in mice to find out how they may use the brand new discovery to develop preventative therapies for coronary heart illness, beginning with exploring whether or not having extra of the AIMP3 protein would assist the center to higher address stress.
Heart problems is the main reason for demise worldwide, Accornero famous.
“The guts is a essential system to review, as a result of there is not actually an efficient technique to restore harm,” she mentioned. “So the upkeep of the well being of those cardiac cells is a very essential level.”
Extra info:
Anindhya S. Das et al, AIMP3 maintains cardiac homeostasis by regulating the enhancing exercise of methionyl-tRNA synthetase, Nature Cardiovascular Analysis (2025). DOI: 10.1038/s44161-025-00670-w
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Molecular-level discovery factors to coronary heart protein AIMP3 as potential goal for brand spanking new cardiac therapies (2025, June 25)
retrieved 25 June 2025
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