CD47 antibody protects mice from doxorubicin‑induced myocardial damage by suppressing cardiomyocyte apoptosis

Hao,Yan; Chen,Lianghua; Jiang,Zhilong

doi:10.3892/etm.2022.11277

CD47 antibody protects mice from doxorubicin‑induced myocardial damage by suppressing cardiomyocyte apoptosis

Authors:
- Yan Hao
- Lianghua Chen
- Zhilong Jiang
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Affiliations: Department of Cardiology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, P.R. China, Department of Pulmonary Medicine, Zhongshan Hospital Affiliated to Fudan University, Shanghai 200032, P.R. China
Published online on: March 24, 2022 https://doi.org/10.3892/etm.2022.11277
Article Number: 350
Copyright: © Hao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Cluster of differentiation 47 (CD47) is upregulated in mouse models of doxorubicin (Dox)‑induced dilated cardiomyopathy (DCM). To explore the role of CD47 in the development of DCM, in the present study, CD47 signaling was blocked by an anti‑CD47 neutralizing antibody (aCD47) in mice with Dox‑induced DCM. Intraperitoneal (i.p.) administration of 10 mg/kg Dox once a week significantly induced the development of DCM after 4 weeks, which was accompanied by the upregulation of CD47 expression in heart tissues. However, co‑administration of Dox with 7 mg/kg aCD47 once a week significantly reduced the severity of DCM, with lower numbers of disordered and broken myofibers, reduced cardiomyocytes and infiltration of macrophages in the heart tissues of treated mice. The beneficial effects were associated with the reduced population of Annexin V+7‑AAD‑ apoptotic cells, and the attenuated formation of interstitial fibrosis and release of lactate dehydrogenase (LDH) in the aCD47‑treated mice. In addition, co‑administration with aCD47 effectively reduced the expression of Bax, collagen I, interleukin (IL)‑6 and tumor necrosis factor (TNF)‑α in murine DCM. These results were further supported by an in vitro study, in which aCD47 pre‑treatment significantly reduced the Dox‑induced early apoptosis of cardiomyocytes and suppressed the expression of Bax, cleaved caspase‑1/3 and phosphorylation of p38 MAPK. Therefore, aCD47 attenuated DCM in mice, possibly by suppressing cardiomyocyte early apoptosis and p38 MAPK signaling. CD47 may be a useful therapeutic target in the treatment of DCM.

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