In a mouse model of heart failure (HF), cardiac stress mediates epigenetic changes in haematopoietic stem cells (HSCs) that promote the generation of pro-inflammatory macrophages and contribute to kidney and skeletal muscle injury. This finding, published in Science Immunology, suggests that an innate immune memory in HSCs might be involved in HF recurrence and associated multimorbidity.

To establish whether HF can modulate HSCs to induce cardiac dysfunction, bone marrow from mice with HF (transverse aortic constriction (TAC) model) were transplanted into healthy mice. At 4 months after the transplantation, these mice showed impaired cardiac function and increased fibrosis compared with control mice. Furthermore, transplantation of bone marrow from TAC mice increased the vulnerability of the kidneys and skeletal muscle to injury in the recipient mice. Cardiac pressure overload induced by TAC seemed to modulate the differentiation potential of HSCs by promoting the generation of pro-inflammatory macrophages rather than cardiac tissue-resident macrophages. This shift in differentiation potential has implications for cardiac homeostasis and remodelling, given that cardiac tissue-resident macrophages are involved in maintaining homeostasis and mediating adaptive stress responses in the heart.