New research suggests that the stress of heart failure can lead to recurrent failure and other related health issues. Heart failure leaves a “stress memory” in hematopoietic stem cells, which produce blood and immune cells called macrophages. During heart failure, a key signaling pathway called transforming growth factor beta (TGF-β) is suppressed in these stem cells, negatively impacting macrophage production and overall heart health. Improving TGF-β levels could be a potential new treatment for recurrent heart failure, while detecting accumulating stress memory could serve as an early warning system.
Global efforts to improve health and well-being have led to a projected increase in life expectancy by approximately 4.5 years by 2050. Despite this progress, heart disease remains the leading cause of death worldwide, affecting an estimated 26 million people with heart failure. The recurrence of heart failure, along with other health issues like kidney and muscle problems, presents a challenge for researchers seeking to understand the mechanisms behind these occurrences and how they can be prevented.
Studying mice with heart failure, researchers found evidence of stress imprinting on the DNA of hematopoietic stem cells, leading to the production of dysfunctional immune cells. The suppression of the TGF-β signaling pathway in these stem cells played a crucial role in this process, contributing to the development of heart failure and organ damage in mice. This “stress memory” persisted over time, suggesting that the stress experienced during heart failure continues to affect the entire body.
By identifying changes in the TGF-β signaling pathway, researchers have identified potential new pathways for future treatments to prevent the accumulation of stress memory during heart failure. Supplementing active TGF-β has shown promise as a potential treatment in animals with heart failure, while correcting the epigenome of hematopoietic stem cells could help deplete stress memory. The researchers hope to develop a system that can detect and prevent stress memory accumulation in humans, with the goal of preventing heart failure recurrence and potentially catching the condition before it fully develops.
Understanding the impact of stress memory from heart failure on hematopoietic stem cells opens up new possibilities for treating and preventing recurrent heart failure. By targeting the TGF-β signaling pathway and correcting epigenetic changes in stem cells, researchers are exploring new avenues for potential therapies. Detecting and preventing stress memory accumulation in humans could be a game-changer in reducing the burden of heart failure and improving outcomes for individuals at risk.
