Reference - Detail
| RRC ID | 86888 |
|---|---|
| Author | He R, Kadyrov FF, Koenig AL, Ma P, Bredemeyer A, Chan MM, Schilling JD, Das S, Lagas JS, Kreisel D, Weinheimer CJ, Nigro JM, Kovacs A, Mosammaparast N, Lavine KJ. |
| Title | DNA-damaging chemotherapy reshapes cardiac-resident macrophage composition and function. |
| Journal | Sci Immunol |
| Abstract |
Heart failure and ischemic heart disease represent prevalent causes of death among cancer survivors. Despite extensive use of conventional chemotherapies, a limited understanding of how these agents affect the cardiac immune landscape exists. Using mouse models, we show that DNA-damaging agents selectively deplete cardiac-resident macrophages through activation of p53 signaling and resultant necroptosis and apoptosis. Genetic lineage tracing, transcriptomic profiling, and functional studies revealed that recruited monocytes progressively reconstitute the cardiac-resident macrophage compartment, were transcriptionally distinct from embryonic-derived cardiac-resident macrophages, and conferred protection from subsequent hypertensive and ischemic cardiac injury in mice. Monocyte-derived resident-like cardiac macrophages suppressed inflammation and attenuated adverse myocardial remodeling through a type I interferon-dependent mechanism. Collectively, these findings highlight unrecognized effects of DNA-damaging chemotherapies on the cardiac immune landscape and shed light on our understanding of monocyte plasticity and resident macrophage dynamics. |
| Volume | 11(115) |
| Pages | eadu4944 |
| Published | 2026-1-2 |
| DOI | 10.1126/sciimmunol.adu4944 |
| PMID | 41481697 |
| MeSH | Animals Antineoplastic Agents* / pharmacology DNA Damage* / drug effects Macrophages* / drug effects Macrophages* / immunology Male Mice Mice, Inbred C57BL Monocytes / immunology Myocardium* / immunology Myocardium* / pathology Tumor Suppressor Protein p53 / metabolism |
| Altmetric score |
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| The most frequently cited source | X(Twitter) |
| Total number of mentions | 53 |
| Altmetric score changes over past 6months | 22.7 |
| Resource | |
| Mice | RBRC04395 |