Human Single-Nucleus RNA Sequencing Identifies CD47 as a Therapeutic Target for Doxorubicin-Induced Cardiomyopathy
Authors' conclusion
Our data support CD47 as a disease-specific target and promising therapeutic approach for mitigating cardiac dysfunction in DoxCM.
Study context
- Population
- LV myocardial tissue from patients with doxorubicin cardiomyopathy (DoxCM), nonischemic cardiomyopathy and nonfailing donors; murine models incl. breast cancer model
- Comparison
- DoxCM vs nonischemic cardiomyopathy and nonfailing donors; CD47 antibody neutralization in murine models
Methodological detailsSingle-nucleus RNA sequencing; validation by immunostaining, flow cytometry, antibody neutralization and cell depletion studies
- Single-nucleus RNA sequencing; validation by immunostaining, flow cytometry, antibody neutralization and cell depletion studies
Main finding
As reported in the abstract
- DoxCM LV myocardium: increased POSTN+ activated fibroblasts, downregulated phagocytosis genes, increased antiphagocytic CD47 vs nonfailing donors and nonischemic cardiomyopathy
- Increased POSTN+ cells and CD47 in human DoxCM sections and in a murine breast cancer model
- CD47 antibody neutralization prevented and treated doxorubicin-induced reduction in LVEF and fibrosis
- Depletion of resident cardiac macrophages blocked the cardioprotective effects of CD47 neutralization and clearance of cardiac fibroblasts
Original publication
Human Single-Nucleus RNA Sequencing Identifies CD47 as a Therapeutic Target for Doxorubicin-Induced Cardiomyopathy. Circulation. Published 14 August 2025. doi:10.
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