Team Finds Protein That Could Help Failing Hearts Recover

Researchers have identified a key protein that may help failing hearts regain function, offering new insight into why some hearts recover while others do not.

This article was written by John Pastor and originally published by Futurity.

The discovery comes from studying patients treated with left ventricular assist devices, or LVADs, which are mechanical pumps that reduce strain on the heart and allow it to rest and recover.

While these devices can stabilize patients with advanced heart failure, only a subset experience meaningful recovery, and the biological reasons have remained unclear.

In a new study in the Journal of the American Heart Association, cardiovascular molecular researcher Junco Warren of Virginia Tech and cardiologist Stavros Drakos of the University of Utah found that a protein called PERM1 is fully restored in patients whose hearts recover after LVAD support. Patients who did not recover showed no such restoration.

The study brought together scientists at Virginia Tech’s Fralin Biomedical Research Institute at VTC and clinical collaborators at the University of Utah, combining molecular research with patient-based cardiac care.

Heart failure affects more than 6 million people in the United States, and predicting recovery remains a major challenge in care.

“This is the first muscle-specific molecular signal linked to recovery in human heart failure,” says Warren, assistant professor at the Fralin Biomedical Research Institute and co-corresponding author.

“We don’t yet know whether PERM1 drives recovery or reflects it, but it gives us a clear window into the biology of how recovery happens.”

The research team analyzed heart tissue from 19 patients, comparing samples collected before and after LVAD implantation. Patients were enrolled through the University of Utah cardiac transplant program, with tissue collected from the left ventricular apex during implantation and later during device removal or transplantation. Patients were categorized as responders or non-responders based on improvements in heart function.

Before treatment, PERM1 levels were reduced in all patients. After LVAD support, levels were restored to near-normal only in those whose hearts recovered, while remaining suppressed in non-responders.

“This study begins to explain why some patients recover heart function with LVAD support while others do not,” says Drakos, professor of cardiology at the University of Utah and co-corresponding author. “Identifying the biological signals behind recovery is essential to improving outcomes for patients with advanced heart failure.”

The findings showed a strong correlation between PERM1 levels and improved cardiac function. PERM1 regulates how heart cells produce and use energy, and recovery was associated with normalization of stress-related metabolic pathways.

Together, the results position PERM1 as both a potential biomarker and a target for future therapies.

“Current therapies help manage heart failure, but they do not repair the heart muscle itself,” says Warren, who is also an assistant professor in Virginia Tech’s human nutrition, foods, and exercise department in the College of Agriculture and Life Sciences.

“Our findings point to a pathway that directly targets cardiomyocytes—the heart muscle cells—and restores both energy production and contractile function, the two core deficits in heart failure.”

Previous work from Warren’s lab showed that increasing PERM1 improves heart function in experimental models. The approach has also been shown to prevent heart failure in preclinical studies and may support recovery in advanced disease, including in patients receiving mechanical heart support.

“Heart failure creates a vicious cycle where energy loss and reduced contraction reinforce each other,” Warren says. “PERM1 appears to act at the center of that cycle.”

While more research is needed to determine whether PERM1 directly causes recovery, the findings provide a step toward new treatment strategies.

To help advance these discoveries toward patient use, Warren and members of her research team have co-founded a company focused on developing PERM1-based gene therapies.

The study was supported by the National Institutes of Health, the American Heart Association, the US Department of Veterans Affairs, the Nora Eccles Treadwell Foundation, and internal funding from the Fralin Biomedical Research Institute.

Source: Virginia Tech