| Autor: |
Nakayama, Yukiteru, Fujiu, Katsuhito, Oshima, Tsukasa, Matsuda, Jun, Sugita, Junichi, Matsubara, Takumi James, Liu, Yuxiang, Goto, Kohsaku, Kani, Kunihiro, Uchida, Ryoko, Takeda, Norifumi, Morita, Hiroyuki, Xiao, Yingda, Hayashi, Michiko, Maru, Yujin, Hasumi, Eriko, Kojima, Toshiya, Ishiguro, Soh, Kijima, Yusuke, Yachie, Nozomu |
| Předmět: |
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| Zdroj: |
Science Immunology; 2024, Vol. 9 Issue 95, p1-15, 15p |
| Abstrakt: |
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." 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. —Claire Olingy [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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