New Insights into Cellular Stress Response: A Potential Target for Heart Failure Treatment

Researchers from the German Center for Cardiovascular Research (DZHK) have uncovered a significant molecule involved in a form of heart failure known as HFpEF (heart failure with preserved ejection fraction), which has historically proved resistant to targeted therapies. HFpEF occurs when the heart pumps normally but still fails to supply sufficient blood to meet the body's needs, a condition increasingly prevalent among individuals with obesity and hypertension.

The study, led by Professor Johannes Backs at Heidelberg University Hospital, focuses on the enzyme nicotinamide nucleotide transhydrogenase (NNT), located in the mitochondria—the energy-producing structures within cells. NNT plays a crucial role in balancing energy production and protecting cells from oxidative stress caused by free radicals. The research reveals that NNT's activity influences the development of HFpEF by mediating the heart's response to metabolic stresses.

By utilizing a mouse model, scientists found that animals deficient in functional NNT exhibited remarkable resistance to developing HFpEF, despite displaying typical risk factors such as obesity, high blood pressure, and glucose intolerance. This provides compelling evidence that NNT is central to the pathological remodeling of the heart muscle involved in HFpEF. Moreover, the study identified the growth factor FGF1, which is activated by NNT, as being associated with the stiffening of the heart muscle—a key feature of HFpEF.

These findings open promising avenues for developing targeted treatments aimed at inhibiting NNT. Such therapies could potentially mitigate or halt the progression of this complex and often challenging form of heart failure. The research underscores the importance of understanding individual cellular responses to metabolic stress and highlights NNT as a potential therapeutic target for improving heart failure outcomes.

This groundbreaking study has been published in Circulation Research and offers hope for more effective management strategies for patients suffering from HFpEF, which currently lacks specific targeted therapies.

Source: https://medicalxpress.com/news/2025-07-cellular-stress-response-potential-therapeutic.html