Protein linked to chronic heart failure discovered

Scientists have identified a receptor protein on the surface of heart cells that promotes chronic heart failure, a discovery that may help treat the disease that affects over 20 million people worldwide.

A team of researchers led by Mikito Takefuji from Nagoya University in Japan discovered that a signalling protein called corticotropin releasing hormone receptor 2 (Crhr2) is expressed on the surface of heart muscle cells, or cardiomyocytes, and that Crhr2 levels increase in mice suffering from heart failure.

Chronic heart failure is caused by a variety of conditions that damage the heart, including coronary heart disease, hypertension, and diabetes.

Crhr2 is a G protein-coupled receptor whose ability to alter cardiomyocyte function is activated by a protein called urocortin 2 (Ucn2), researchers said.

They found that Ucn2 levels were elevated in the blood of both mice and human patients with chronic heart failure.

Sustained treatment of otherwise healthy mice with Ucn2 was sufficient to reduce cardiac function, researchers said.

Researchers found that the activation of Crhr2 by Ucn2 stimulates several downstream signalling pathways that result in the expression of genes that impair heart function.

Mice lacking Crhr2 were protected from the effects of Ucn2 and were resistant to developing heart failure. A small molecule that inhibits Crhr2 was similarly effective in maintaining cardiac function after damage to the heart.

The G protein-coupled receptors such as Crhr2 are considered to be relatively easy to target with specific drugs, researchers said.

"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," Takefuji said.

The study was published in The Journal of Experimental Medicine.

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