Targeting an atypical G protein–coupled receptor signaling pathway for cardiac fibrosis therapy

Editor’s summary

Cardiovascular disease is the world’s leading cause of death, and cardiac fibrosis plays a key role in the pathology of many types of cardiovascular disease. Once fibrosis sets in at the site of cardiac injury, it causes tissue stiffening and impaired function, and there are no approved treatments to reverse this state. Using a high-throughput drug discovery pipeline followed by validation in human stem cell–derived cardiac cells and tissues and mouse models, Zhang et al. identified a potential intervention. The researchers characterized an adenosine receptor–dependent signaling axis that promotes fibrosis. They also discovered a compound that can inhibit this pathway both in vitro and in vivo and may also work in organs other than the heart. —Yevgeniya Nusinovich