ArticleCirculation2025
Human Single-Nucleus RNA Sequencing Identifies CD47 as a Therapeutic Target for Doxorubicin-Induced Cardiomyopathy.
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Article in Circulation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed.
- CD47 is a regulator in doxorubicin-induced cardiac aging in male mice.Physiological reports · 2026Article
- Chemotherapy-Activated GSK3β-DNMT1 Signaling Upregulates CD47 to Evade Macrophage Phagocytosis and Drive Temozolomide Resistance in Glioblastoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Article
- Ultrasound-Triggered Nanobubbles for Endothelial-Targeted Drug Delivery in the Detection and Treatment of Doxorubicin-Induced Cardiotoxicity.Advanced healthcare materials · 2026Article
- Multimodality Molecular Profiling Nominates Targetable Mechanisms in Progressive RV Dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Mitochondrial dysfunction-driven PANoptosis in doxorubicin-induced cardiotoxicity: mechanistic insights and intervention strategies.Frontiers in pharmacology · 2026Review
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Authors and funding
38 authors.
Zhen Guo *Department of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-8421-4852
Anahita Ataran *Department of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0003-4426-4959
Pan MaDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-0815-849X
Wenjing YuDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0009-0004-5356-4034
Hamidreza HajirezaeiDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0001-9023-4262
Carla Valenzuela RipollDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-6177-5227
Lauren N PedersenDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0003-0313-3311
Omid RashidiDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.
Mandy M ChanDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0001-6511-0962
Mengcheng ShenDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0001-7037-6159
Shannon KelleyDepartment of Pathology & Immunology, Division of Biology & Biomedical Sciences (S.K., K.S.R.), Washington University School of Medicine, St Louis, MO.
Alireza SargaziDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.
Mualla OzcanDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-1763-5454
Aynaz LotfinaghshDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0009-0005-8712-2020
Yoonje ChoDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0001-9641-8572
Ahmed DiabDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-1891-3620
Felicia GroganDepartment of Radiation Oncology (F.G., A. Klaas, J.S., C.B.), Washington University School of Medicine, St Louis, MO.
Amanda KlaasDepartment of Radiation Oncology (F.G., A. Klaas, J.S., C.B.), Washington University School of Medicine, St Louis, MO.
Alexander PompianDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.
Adnan ImamDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0009-0003-7499-4941
Rehman LodhiDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0009-0009-4470-6797
Amen Bekele ZellekeDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.
Attila KovacsDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.
Kenneth B MarguliesPenn Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania School of Medicine/Hospital of the University of Pennsylvania, Philadelphia (K.B.M.).ORCID 0000-0002-8093-4465
Jeff SzymanskiDepartment of Radiation Oncology (F.G., A. Klaas, J.S., C.B.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-8005-701X
Marco SardielloDepartment of Pediatrics, Division of Genetics & Genomic Medicine (M. Sardiello), Washington University School of Medicine, St Louis, MO.
Babak RazaniDepartment of Medicine, Division of Cardiology, University of Pittsburgh School of Medicine, Pittsburgh, PA (B.R.).ORCID 0000-0002-7172-9240
Aarti AsnaniBeth Israel Deaconess Medical Center, Beth Israel and Harvard Medical School, Boston, MA (A. Asnani).ORCID 0000-0003-4967-9918
Benjamin J KopeckyDivision of Cardiology, University of Colorado School of Medicine, Aurora (B.J.K.).ORCID 0000-0002-9087-6254
Pierre E SignoreBitterroot Bio, Palo Alto, CA (P.E.S., B.A.Y., C.T.B.).
B Alexander YiBitterroot Bio, Palo Alto, CA (P.E.S., B.A.Y., C.T.B.).ORCID 0000-0003-4888-2391
Craig T BassonDepartment of Radiation Oncology (F.G., A. Klaas, J.S., C.B.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0003-0211-4936
Kodi S RavichandranDepartment of Pathology & Immunology, Division of Biology & Biomedical Sciences (S.K., K.S.R.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0001-9049-1410
Sumanth D PrabhuDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-7247-7241
Carmen BergomDepartment of Radiation Oncology (F.G., A. Klaas, J.S., C.B.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-0886-5055
Joel D SchillingDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0002-3884-1994
Kory J LavineDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0003-1948-9945
Ali JavaheriDepartment of Medicine, Division of Cardiology (Z.G., A.Ataran, P.M., Y.W., H.H., C.V.R., L.N.P., O.R., M.M.C., M.Shen, A.S., M.O., A.L., Y.C., A.D., A.P., A.I., R.L., A.B.Z., A.Kovacs, S.D.P., J.D.S., K.J.L., A.J.), Washington University School of Medicine, St Louis, MO.ORCID 0000-0001-6657-331X
Funding
Washington University DDRCC Supplemental Equipment RequestP30DK052574 · NIDDK · WASHINGTON UNIVERSITY · PI Jeffrey Wade Brown · 2000 to 2026
$30.8MWashington University Nutrition Obesity Research CenterP30DK056341 · NIDDK · WASHINGTON UNIVERSITY · PI Dominic N Reeds · 1999 to 2026
$30.2MWU P&FP30DK020579 · NIDDK · WASHINGTON UNIVERSITY · PI Clay F. Semenkovich · 2013 to 2026
$27.1MPRINCIPLES IN CARDIVASCULAR RESEARCH TRAINING PROGRAMT32HL007081 · NHLBI · WASHINGTON UNIVERSITY · PI Abhinav Diwan, Karen Ellen Joynt Maddox · 1985 to 2026
$10.6MIntegrative genomics of human heart failureR01HL105993 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI ASHLEY, EUAN A, CAPPOLA, THOMAS P. · 2011 to 2014
$8.9MSpecification and Function of Tissue Resident and Recruited Macrophages in Cardiac Remodeling and Heart FailureR35HL161185 · NHLBI · WASHINGTON UNIVERSITY · PI Kory J. Lavine · 2022 to 2026
$4.3MMechanical Stress-Dependent Remodeling of the Cardiac Microtubule NetworkR01HL149891 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Kenneth Ber Margulies, Benjamin Lears Prosser · 2020 to 2026
$4.2MApolipoprotein M: a novel regulator of myocardial AutophagyR01HL155344 · NHLBI · WASHINGTON UNIVERSITY · PI JAVAHERI, ALI · 2021 to 2025
$3.1MThe Role of Donor Innate Immune Responses in Regulating Alloimmunity after Heart TransplantationR01HL151078 · NHLBI · WASHINGTON UNIVERSITY · PI KREISEL, DANIEL, LAVINE, KORY J. · 2020 to 2023
$2.6MGenetic Modifiers of Radiation Therapy-Induced CardiotoxicityR01HL147884 · NHLBI · WASHINGTON UNIVERSITY · PI BERGOM, CARMEN · 2019 to 2023
$2.3MEndogenous Cardiac Repair in HumansR01HL089847 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI MARGULIES, KENNETH BER · 2009 to 2012
$1.9MHARNESSING THE LYSOSOME MACHINERY IN MACROPHAGES TO PREVENT HEART FAILUREK08HL138262 · NHLBI · WASHINGTON UNIVERSITY · PI JAVAHERI, ALI · 2017 to 2021
$752kNHLBI NIH HHS K08 HL138262NHLBI NIH HHS K99 HL166693NHLBI NIH HHS K99 HL171935NHLBI NIH HHS R01 HL089847NHLBI NIH HHS R01 HL105993NHLBI NIH HHS R01 HL147884NHLBI NIH HHS R01 HL149891NHLBI NIH HHS R01 HL151078NHLBI NIH HHS R01 HL155344NHLBI NIH HHS R35 HL161185NHLBI NIH HHS T32 HL007081NIDDK NIH HHS P30 DK020579NIDDK NIH HHS P30 DK052574NIDDK NIH HHS P30 DK056341NIH HHS S10 OD020136NIH HHS S10 OD028597
Abstract
backgroundDoxorubicin cardiomyopathy (DoxCM) remains a significant clinical problem, but its underlying mechanisms remain incompletely understood. Identifying DoxCM mechanisms can lead to therapeutic interventions that improve patient outcomes.
methodsWe performed single-nucleus RNA sequencing on left ventricular myocardial tissue from patients with DoxCM versus nonischemic cardiomyopathy and nonfailing donors. This approach aimed to uncover the transcriptional changes associated with DoxCM. Additionally, we conducted immunostaining, flow cytometry, antibody neutralization, and cell depletion studies to validate our findings and define in vivo mechanisms.
resultsCompared with nonfailing donors and patients with nonischemic cardiomyopathy, left ventricular myocardium from patients with DoxCM exhibited increased POSTN (periostin)
conclusionsOur data support CD47 as a disease-specific target and promising therapeutic approach for mitigating cardiac dysfunction in DoxCM.
Indexed as
Antibiotics, AntineoplasticCardiomyopathiesCD47 AntigenDoxorubicinAnimalsAntibodies, NeutralizingDisease Models, AnimalFemaleHeart VentriclesHumansMacrophagesMaleMiceMice, Inbred C57BLMyocardiumPeriostinAntibiotics, AntineoplasticAntibodies, NeutralizingCD47 AntigenDoxorubicinPeriostinactivated fibroblastsCD47doxorubicin cardiomyopathyresident macrophage
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