Recent research has unveiled a significant discovery in the field of heart health. It has been found that heart failure induces lasting physiological stress, potentially contributing to recurrent health issues. This is not just a temporary effect, but a ‘stress memory’ phenomenon that persists in hematopoietic stem cells, the cells responsible for blood and immune cell production, particularly macrophages crucial for heart health. During heart failure, the DNA modifications of these stem cells are altered, affecting the transformative growth factor beta (TGF-β) pathway. Suppressed TGF-β levels hinder macrophage production, exacerbating heart failure and associated complications. The implications of this ‘stress memory’ are profound, offering a promising strategy for mitigating recurrent heart failure, with potential applications in the early detection of stress accumulation.
Global efforts towards sustainable development goals, including improved health and well-being, yield positive outcomes, with life expectancy projected to rise by approximately 4.5 years by 2050. Public health initiatives have significantly reduced disease incidence and mortality rates, particularly for cardiovascular diseases. Despite these advances, heart disease remains the world’s leading cause of death, affecting an estimated 26 million people through conditions like heart failure.
Researchers in Japan have focused on understanding the mechanisms underlying heart failure recurrence and associated organ deterioration. Their investigations suggest that stress accumulated during heart failure, specifically in hematopoietic stem cells, may play a pivotal role. Project Professor Katsuhito Fujiu from the University of Tokyo’s Graduate School of Medicine highlights the role of these stem cells in the bone marrow and responsible for immune cell production. Studies in mice with heart failure reveal epigenetic changes in DNA, including suppression of the TGF-β pathway in hematopoietic stem cells, leading to dysfunctional immune cell production.
This stress-induced ‘memory’ persists over time, as demonstrated by experiments in which bone marrow transplanted from mice with heart failure perpetuated dysfunctional immune cell production and increased susceptibility to heart failure and organ damage in recipient mice. Fujiu describes this phenomenon as ‘stress memory’, wherein the effects of heart failure stress continue to influence the body long after the initial episode, potentially exacerbating future health challenges.
Excitingly, the identification of these epigenetic changes in the TGF-β pathway has opened new avenues for therapeutic interventions. Project Professor Katsuhito Fujiu from the University of Tokyo’s Graduate School of Medicine suggests innovative treatments that could potentially revolutionize the management of heart failure. These treatments aim to prevent stress memory accumulation during heart failure hospitalization, such as supplementing active TGF-β to restore normal signalling and correcting the epigenome of hematopoietic stem cells. These strategies hold the promise of not only preventing recurrent heart failure but also intercepting its development before significant symptoms arise, offering a beacon of hope for the future of heart health.
The research team aims to develop diagnostic tools capable of detecting and mitigating stress memory in human patients. Their ultimate goal is to enhance early intervention strategies, transforming the management of heart failure by addressing underlying physiological stressors before they manifest clinically.
More information: Yukiteru Nakayama et al, Heart failure promotes multimorbidity through innate immune memory, Science Immunology. DOI: 10.1126/sciimmunol.ade3814
Journal information: Science Immunology Provided by The University of Tokyo
