Signaling protein could be the target that stops heart failure in its tracks

There is no cure for heart failure, but scientists at Nagoya University have identified a protein on the surface of heart cells that could be targeted to stop the condition from getting worse.

Heart failure, in which the heart is unable to pump enough blood to support the body, can be caused by a number of conditions, including congenital heart defects and a past heart attack. The heart tries to compensate by growing larger, developing more muscle mass or pumping faster, but the condition grows progressively worse until these stopgaps no longer work.

Physicians usually advise patients to embrace lifestyle changes and prescribe drugs such as beta blockers. Medical devices, including implantable cardioverter defibrillators, are also widely used. But these measures cannot reverse the damage that's already done.

The Nagoya team found that heart cells express the signaling protein, corticotropin-releasing hormone receptor 2 (Crhr2), on their surface, according to a press release. Crhr2 is a G protein-coupled receptor: It detects molecules outside cells and activates pathways inside the cell, which leads to a cellular response.

The researchers discovered that mice with heart failure had elevated levels of Crhr2. They also found that human patients and mice with chronic heart failure had high levels of the protein urocortin2 (Ucn2) in their blood.

They treated mice with Ucn2 and noticed that otherwise healthy mice with Crhr2 lost cardiac function, while mice that lacked the signaling protein were resistant to developing heart failure. A Crhr2 inhibitor delivered after the heart sustained damage preserved heart function in mice.

While current heart failure treatments focus on preserving function, about half of all people who develop heart failure will die within five years of diagnosis, according to the CDC. That's why many scientists are working to improve upon today's treatments.

“Our results suggest that constitutive Crhr2 activation causes cardiac dysfunction and that Crhr2 blockade could be a promising therapeutic strategy for patients with chronic heart failure,” said Mikito Takefuji of Nagoya University Medical School in the statement.