Published August 22, 2017 | Journal of the American College of Cardiology

The small-molecule compound gallein helps reduce major symptoms of heart failure in mice by blocking signals sent by a protein that helps regulate the heart’s response to adrenaline—a discovery that eventually may shift treatment approaches for one of the nation’s leading causes of death.

Heart failure affects about 5.7 million U.S. adults, with about half of those people dying within five years of diagnosis, according to the Centers for Disease Control and Prevention. But a study led by first author Joshua Travers, PhD, and senior author Burns Blaxall, PhD, reports preclinical success at slowing post-heart attack fibrosis and hypertrophy.

The treatment alleviated disease processes in mouse models of human heart failure and in cardiac cells from heart failure patients undergoing surgery.

The team focused on molecular signaling between the proteins Gbg and GRK2, a signaling pathway activated by adrenaline stimulation. The adrenergic system supports normal heart function, but chronic over-stimulation after a heart attack prompts scar tissue formation and hypertrophy—-a thickening and enlargement of heart muscle.

When started in mouse models one week after initial cardiac injury, gallein reduced pathological fibrosis and rescued the animals from heart failure. Similar protection also occurred in a new line of mice in which GRK2 was removed from the cardiac fibroblast, suggesting target specificity.

“Regrettably, there are essentially no clinical interventions that effectively target these tissue-damaging cardiac fibroblasts. This work may provide evidence that shifts the way we think about treating heart failure and organ fibrosis,” says Blaxall,  Director of the institute’s Center for Translational Fibrosis Research.

Looking ahead, the researchers are collaborating with other institutions to develop a gallein-like compound for eventual human testing. They also plan to explore fibrotic remodeling in other tissues such as the lung, liver, and kidney.