West LA Times

UCLA researchers have discovered a significant role for the protein GPNMB in heart repair following a heart attack. The study, using animal models, found that macrophages—immune cells derived from bone marrow—secrete GPNMB. This protein then binds to the receptor GPR39, facilitating heart repair. These findings could pave the way for new treatments to improve heart function and prevent progression to heart failure.

Heart attacks occur every 40 seconds in the United States and are a leading cause of heart failure. These events damage the heart, causing scarring that impairs its ability to pump blood effectively. While initial scar tissue formation maintains structural integrity, it eventually leads to increased strain on surviving muscle and potential heart failure.

Previous studies linked GPNMB with cardiovascular outcomes in individuals with heart failure but did not clarify if its absence directly contributes to post-heart attack failure development. Determining whether GPNMB is merely an associated biomarker or plays a causal role is crucial for considering it as a therapeutic target.

Researchers used mouse models to establish that GPNMB is produced by inflammatory cells from bone marrow rather than by the heart itself. After a heart attack, these macrophages travel to the injury site in the heart and express GPNMB. Through gene knockouts and bone marrow transplants, they observed that mice lacking GPNMB experienced worse outcomes after a simulated heart attack, including higher incidences of fatal complications like heart rupture.

In contrast, mice with normal GPNMB expression receiving additional doses of circulating protein showed improved cardiac function and reduced scarring. Four weeks post-heart attack simulation, 67% of animals without the GPNMB gene exhibited severe fibrosis compared to only 8% in control groups.

The research identified GPNMB as a signaling molecule affecting various cell types by binding with previously orphaned receptor GPR39. This interaction triggers signals promoting tissue regeneration and limiting scarring.

Cardiovascular disease remains a major health concern globally, accounting for about one-third of all deaths worldwide. Current treatments do not enhance cardiac self-repair after an attack; however, this study highlights the potential of using both GPNMB as a therapeutic agent and targeting receptor GPR39 for reducing scarring and improving cardiac function.

The implications extend beyond cardiac repair; since GPNMB is expressed in multiple tissues, future research will explore its role in repairing other organs affected by ischemic injury such as brain or kidneys.

Dr. Arjun Deb led this study published in Nature Cardiovascular Research with funding from National Institutes of Health grants. It should be noted that while promising results have been observed preclinically regarding therapeutic use involving human trials still require assessment regarding safety efficacy considerations.