HMN 2025: How modified protein can aid heart attack recovery

A preclinical study led by the Smidt Heart Institute at Cedars-Sinai challenges the assumption that blocking the NCX1 protein, which regulates calcium levels in cells, is more effective than maintaining its activity during a heart attack to limit damage.

The findings, published in the Proceedings of the National Academy of Sciences, suggest that preserving the function of the protein could even be more beneficial.

Investigators used gene editing to create a mutant version of NCX1 in laboratory mice. This mutation allowed the protein to function despite changes in acidity that are produced during heart attacks. The modified mice maintained better calcium balance and heart function and showed significantly less cardiac injury after heart attacks than did mice with the unaltered protein.

“Our findings suggest that maintenance of NCX1 activity should be considered as a strategy for clinicians to reduce cardiac injury in patients,” said Joshua I. Goldhaber, MD, the Dorothy and E. Phillip Lyon Chair in Laser Research, professor of Cardiology and Biomedical Sciences and vice dean of Graduate Education at Cedars-Sinai.

“They also form the basis for future studies of calcium regulation in the body. We showed that acid regulation of NCX1 is important for maintaining calcium balance in heart cells.”