Stress memory in heamatopoietic stem mcells
Heart failure progresses through a series of acute exacerbations of heart failure. It also promotes other diseases such as chronic kidney disease, sarcopenia and cancer. It is also reciprocally affected by these diseases, causing further disease deterioration. We have shown that hematopoietic stem cells (HSCs) carry a memory of heart failure that affects not only heart failure but also other diseases and promotes multimorbidity. HSCs are the cells that make blood cells in the body. These cells were found to be altered in heart failure, and the resulting HSC-derived macrophages altered their function from being tissue-protective to promoting inflammation and compromising tissue function, leading to heart failure, CKD and sarcopenia. We also found that the stress of heart failure impairs the sympathetic nerves that go to the bone marrow and inscribe memory in hematopoietic stem cells. These findings not only revealed a novel mechanism by which heart failure and its comorbidities progress, but also led to the identification of mechanisms and molecules for new therapeutic and diagnostic targets.
