2026/01/02 by Ruijun He, Farid F. Kadyrov, Andrew L. Koenig +12 · 1 voice
Medicine · Immunology and Microbiology · Biochemistry, Genetics and Molecular Biology · #Cardiac Fibrosis and Remodeling #Immune cells in cancer #Congenital heart defects research
paper · doi:10.1126/sciimmunol.adu4944
openalex publication_date 2026/01/02 · openalex created_date 2026/01/02 · openalex updated_date 2026/07/31
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.