Penn researchers discover proteins that could prevent heart failure after heart attack

Researchers from the University of Pennsylvania have discovered new evidence that could help explain why patients who’ve suffered heart attacks go into heart failure.

Heart failure often develops after a heart attack because of a long-term damage response by the immune system that transforms some heart muscle into stiff, fibrous, scar-like tissue. But the new study, published Feb. 7 in the Journal of Clinical Investigation, has identified a set of signaling proteins produced in the epicardium that play a role in keeping the immune system response in check.

"These findings highlight the importance of the heart's interaction with the immune system in the post-heart-attack response," said Rajan Jain, MD, an author on the study and assistant professor of cardiovascular medicine at Penn, in a statement. "They hint at the possibility of developing designer therapies aimed at modulating specific aspects of immune system in the future as part of treating patients who have had a heart attack."

Prior research shows that in the epicardium, a cascade of protein-to-protein interactions known as the Hippo signaling pathway occurs early in life and is vital for normal heart development. Other research has found that two key components of the Hippo pathway, proteins YAP and TAZ, also cause the heart muscle to regenerate after a heart attack.

In the Penn study, conducted on mice, the researchers studied the role of epicardial YAP and TAZ after a heart attack in an adult heart, compared to a fetal or newborn heart. They found the adult heart wasn’t able to regenerate itself as well as the younger ones.

"The hearts of these mice were essentially encased in fibrotic cells," Jain said. "We found that this extreme fibrotic response was accompanied by a decline in heart function resembling what is seen in human heart failure, as well as rapid weight loss and a much higher death rate."

Jain and Jonathan A. Epstein, another author on the study and the executive vice dean and chief science officer at Penn Medicine, plan to execute further experiments to find out the fibrosis-causing immune response in more detail.

"We are hoping to harness the immune system, just as we are doing at Penn to fight cancer, in order to improve the balance between scar formation and regeneration after a heart attack," Epstein said in a statement. "The more we look, the more we discover that the immune system is regulating how we heal from injury in every way—acting like the conductor of a complex cellular orchestra."