Journal article
DNA-damaging chemotherapy reshapes cardiac-resident macrophage composition and function
Science immunology, Vol.11(115), p.eadu4944
01/02/2026
DOI: 10.1126/sciimmunol.adu4944
PMID: 41481697
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.
Details
- Title: Subtitle
- DNA-damaging chemotherapy reshapes cardiac-resident macrophage composition and function
- Creators
- Ruijun He - Washington University in St. LouisFarid F Kadyrov - Washington University in St. LouisAndrew L Koenig - Washington University in St. LouisPan Ma - Washington University in St. LouisAndrea Bredemeyer - Washington University in St. LouisMandy M Chan - Washington University in St. LouisJoel D Schilling - Washington University in St. LouisShibali Das - Washington University in St. LouisJoseph S Lagas - Washington University in St. LouisDaniel Kreisel - Washington University in St. LouisCarla J Weinheimer - Washington University in St. LouisJessica M Nigro - Washington University in St. LouisAttila Kovacs - Washington University in St. LouisNima Mosammaparast - Washington University in St. LouisKory J Lavine - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Science immunology, Vol.11(115), p.eadu4944
- DOI
- 10.1126/sciimmunol.adu4944
- PMID
- 41481697
- ISSN
- 2470-9468
- eISSN
- 2470-9468
- Grant note
- R01 HL138466 / NHLBI NIH HHS R01 HL151078 / NHLBI NIH HHS R01 HL139714 / NHLBI NIH HHS R35 HL161185 / NHLBI NIH HHS
- Language
- English
- Date published
- 01/02/2026
- Academic Unit
- Stead Family Department of Pediatrics
- Record Identifier
- 9985161456602771
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