Advanced Heart Failure Reversed By Newly Discovered Ability for Muscle Cells to Regenerate

Updated | Heart disease, the leading cause of death in the U.S., kills more than 600,000 people each year. Identifying a way to reverse the condition has long been a Holy Grail of medicine. In a groundbreaking study in mice, a team of researchers may have done just that.

Cardiac events cause permanent damage that leads to a risk for heart failure. A heart attack limits the amount of blood oxygen circulating in the heart, and as a result part of the organ’s tissue dies and, eventually, scar tissue develops. That inhibits the ticker's ability to pump blood. Prescription medications, defibrillation, surgery and transplant of a donor organ can prevent  subsequent cardiac events, but these approaches are far from satisfying (see mortality rate above).  

Researchers at Baylor College of Medicine may have identified a better solution. In an early-phase mouse model, they’ve discovered a potential signaling pathway known as Hippo. After a heart attack, this pathway is usually highly active, preventing the muscle cells of the heart from proliferating and regenerating. The researchers hypothesized that turning off this signaling pathway would allow the heart to repair on its own. 

James Martin, professor and Vivian L. Smith Chair in regenerative medicine at Baylor College of Medicine and director of the Cardiomyocyte Renewal Lab at the Texas Heart Institute and lead author on the study, says the ability of the Hippo pathway to control cellular growth in the fruit fly was first reported in 2003. In 2011, he and his fellow researchers demonstrated it was possible to control growth in the developing mouse heart through the Hippo pathway. 

"Over the intervening years we and multiple other labs have published evidence pointing to a role for the pathway in heart regeneration," he tells Newsweek. "The novelty of our current study is that the regenerative effect of removing the pathway extends into a very severe cardiac injury like heart failure."

To test that theory, the researchers induced heart attacks in lab mice in order to mimic heart failure in humans. They then used gene therapy to turn off the Hippo pathway in the animals. Using tests such as echocardiograms, the researchers monitored the mice for the following six weeks to see if their hearts would heal on their own.

And that is exactly what happened. According to the study, published Wednesday in Nature, in time the hearts recovered full function and were able to pump blood as sufficiently as healthy hearts. The mice also had far less scar tissue on the organ, a change that allowed it to function far more effectively. 

Martin says he hopes to move this research forward into the clinic. "First, we want to fully understand the long-term consequences of altering the Hippo pathway."

Research has already shown that the Hippo signaling pathway plays a role in other diseases. Elevated levels of Hippo are seen in patients with certain types of breast, colorectal and liver cancer. But research is only just starting to look at what this signaling pathway means for heart health. 

Updated: This story has been updated to include comments from one of the study's researchers. 

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