The role of sex on the effects of ERBB4 agonists as a treatment for heart failure
Description: Heart failure remains one of the biggest health challenges worldwide. Existing treatments help, but many patients continue to experience serious symptoms, hospitalizations, and reduced quality of life. Researchers at our university are exploring an exciting new direction: activating a natural protective system in the heart called ERBB4. Our team recently discovered the first small molecule, named EF‑1, that can switch on this protective pathway. Unlike similar treatments now being tested in clinical trials, EF‑1 could eventually be taken much more easily, without the need for injections or hospital visits. During early studies in mice, the team made a surprising discovery that EF‑1 protected female hearts much more strongly than male hearts. This difference had never been reported before, and it raises an important question: Why does this promising therapy work better in females? Clues from our experiments, and from research in other organs, suggest that the answer may involve estrogen, the primary female hormone. Estrogen is known to protect the heart before menopause, and our data show that EF‑1 stops working when estrogen levels are removed. When estrogen is added back, its benefits return. This project will explore this connection in depth. The research will: Test whether estrogen levels influence how well EF‑1 and related molecules protect the heart during heart attacks or chemotherapy‑induced heart damage. Study how estrogen and ERBB4 work together inside heart cells to prevent cell death, protect energy production, and limit scarring. Investigate whether both systems physically interact at the molecular level by "co‑activating" the same protective genes. The goal is to understand how hormones shape the heart's response to this new therapy, and why women and men may benefit differently. This knowledge is urgently needed. After menopause, women lose estrogen's natural protection and face a steep rise in heart disease. Yet female patients are still underrepresented in cardiovascular research and often experience delayed diagnosis and worse outcomes. By uncovering how ERBB4 and estrogen cooperate, this project aims to pave the way for more personalized, sex‑specific heart treatments. The findings could guide future therapies not only for women after menopause, but also for anyone whose hormonal balance affects heart health. This research builds on decades of expertise in our university's cardiovascular biology group and supports the broader global effort to reduce the long‑standing gap between male and female outcomes in heart disease.
Funder: Vlaamse regering
Funding type: fellowship
Funder scheme: BOF - doctoral mandates
Start date: 2026-07-01
End date: 2030-06-30
Investigator: Vincent Segers
Institution: UAntwerpen
Funded outputs count: 0
Funder award ID: 56484
OpenAlex ID: G8353360998