Good news! Amazing stuff!
"Heart failure rarely occurs in isolation. Patients with this condition are prone to recurring cardiac problems and frequently develop other conditions, such as kidney disease, that involve chronic inflammation. Now, experiments in mice suggest that this could be because cardiac stress causes lasting changes to cells in bone marrow, and this “memory” makes the heart and other organs more vulnerable to disease.
Changes in cardiac macrophages—immune cells that play a vital role in maintaining heart health—have previously been linked to heart failure, but researchers wondered if the stem cells that give rise to them also play a role in cardiovascular disease. To find out more, they extracted bone marrow from rodents with heart failure and transplanted it into healthy recipients. They found that when these blood stem cells matured into macrophages and settled in the recipient mice’s hearts, they tended to respond poorly to stress. As a result, mice that received these cells began to spontaneously develop heart problems and became susceptible to kidney and muscle damage.
The findings suggest that—at least in mice—bone marrow “serves as a hub for stress responses,” with blood stem cells carrying key “stress memories.” These memories, the researchers note, may be responsible for the comorbidities and repeated episodes of heart failure seen in human patients."
From the editor's summary and abstract:
"Editor’s summary
Heart failure (HF) is often associated with recurrence and the development of comorbidities, but the mechanisms driving multimorbidity in patients with HF are not fully understood. Using a mouse model of HF, Nakayama et al. found that transplantation of bone marrow from these mice spontaneously resulted in cardiac dysfunction in recipient mice. Mice transplanted with HF-experience bone marrow were also more vulnerable to kidney and skeletal muscle injury. HF reprogrammed hematopoietic stem cell differentiation and altered tissue macrophage homeostasis. Together, these finding demonstrate that the bone marrow can carry an innate immune memory of cardiac stress that may exacerbate HF and predispose other organs to pathology. ...
Abstract
Patients with heart failure (HF) often experience repeated acute decompensation and develop comorbidities such as chronic kidney disease and frailty syndrome. Although this suggests pathological interaction among comorbidities, the mechanisms linking them are poorly understood. Here, we identified alterations in hematopoietic stem cells (HSCs) as a critical driver of recurrent HF and associated comorbidities. Bone marrow transplantation from HF-experienced mice resulted in spontaneous cardiac dysfunction and fibrosis in recipient mice, as well as increased vulnerability to kidney and skeletal muscle insults. HF enhanced the capacity of HSCs to generate proinflammatory macrophages. In HF mice, global chromatin accessibility analysis and single-cell RNA-seq showed that transforming growth factor–β (TGF-β) signaling was suppressed in HSCs, which corresponded with repressed sympathetic nervous activity in bone marrow. Transplantation of bone marrow from mice in which TGF-β signaling was inhibited similarly exacerbated cardiac dysfunction. Collectively, these results suggest that cardiac stress modulates the epigenome of HSCs, which in turn alters their capacity to generate cardiac macrophage subpopulations. This change in HSCs may be a common driver of repeated HF events and comorbidity by serving as a key carrier of “stress memory.”"
Fig. 1. Transplantation of BM from TAC mice induces spontaneous cardiac dysfunction.
No comments:
Post a Comment