SLAMF7 Restrains Pro-Inflammatory Macrophage Activation to Counteract Doxorubicin-Induced Cardiotoxicity

doi:10.1016/j.jacbts.2025.02.015

. 2025 May 14:101256.

doi: 10.1016/j.jacbts.2025.02.015. Online ahead of print.

SLAMF7 Restrains Pro-Inflammatory Macrophage Activation to Counteract Doxorubicin-Induced Cardiotoxicity

Ao Liu¹, Peiyuan Bai², Hongmin You³, Zehao Zhuang⁴, Fangyan Tian⁵, Haobo Weng¹, Xuemei Wei¹, Lu Tang⁶, Litao Wang⁷, Chaobao Liu⁸, Jinghong Zhang⁸, Minmin Sun⁶, Shuning Zhang², Xianhong Shu⁹, Junbo Ge¹⁰

Affiliations

¹ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, China.
² Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China.
³ Department of Cardiology, Changhai Hospital, Naval Medical University, Shanghai, China.
⁴ Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China.
⁵ Department of Ultrasound Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
⁶ Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, China.
⁷ Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁸ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁹ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, China. Electronic address: shu.xianhong@zs-hospital.sh.cn.
¹⁰ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China. Electronic address: jbge@zs-hospital.sh.cn.

PMID: 40372307
DOI: 10.1016/j.jacbts.2025.02.015

Free article

SLAMF7 Restrains Pro-Inflammatory Macrophage Activation to Counteract Doxorubicin-Induced Cardiotoxicity

Ao Liu et al. JACC Basic Transl Sci. 2025.

Free article

. 2025 May 14:101256.

doi: 10.1016/j.jacbts.2025.02.015. Online ahead of print.

Authors

Affiliations

¹ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, China.
² Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China.
³ Department of Cardiology, Changhai Hospital, Naval Medical University, Shanghai, China.
⁴ Department of Cardiovascular Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang University, Nanchang, China.
⁵ Department of Ultrasound Medicine, The Affiliated Hospital of Guizhou Medical University, Guiyang, China.
⁶ Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, China.
⁷ Department of Cardiology, the Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁸ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China.
⁹ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China; Department of Echocardiography, Zhongshan Hospital, Fudan University, Shanghai Institute of Cardiovascular Diseases, Shanghai Institute of Medical Imaging, Shanghai, China. Electronic address: shu.xianhong@zs-hospital.sh.cn.
¹⁰ Department of Cardiology, Zhongshan Hospital, Shanghai Institute of Cardiovascular Diseases and Institutes of Biomedical Sciences, Fudan University, Shanghai, China; State Key Laboratory of Cardiology, Zhongshan Hospital, Fudan University, Shanghai, China; NHC Key Laboratory of Ischemic Heart Diseases, Shanghai, China; Key Laboratory of Viral Heart Diseases, Chinese Academy of Medical Sciences, Shanghai, China; National Clinical Research Center for Interventional Medicine, Shanghai, China. Electronic address: jbge@zs-hospital.sh.cn.

PMID: 40372307
DOI: 10.1016/j.jacbts.2025.02.015

Abstract

Doxorubicin-induced cardiotoxicity (DIC) poses a significant challenge in cancer treatment. This study investigated the role of SLAMF7 in DIC, particularly in macrophage-mediated inflammation. Using SLAMF7 knockout mice, we found that SLAMF7 deficiency exacerbates DIC and amplifies inflammatory responses. Mechanistically, SLAMF7 interacts with TNF receptor-associated factor 6 to attenuate nuclear factor κB signaling, reducing oxidative stress and proinflammatory cytokines. Notably, administering recombinant SLAMF7 protein effectively mitigated DIC. These findings underscore the critical role of SLAMF7 in protecting against DIC, positioning it as a promising therapeutic target.

Keywords: NF-κB; SLAMF7; TRAF6; cardiotoxicity; macrophage.

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Conflict of interest statement

Funding Support and Author Disclosures This work was supported by the National Natural Science Foundation of China (T2288101, 82227803, 82071933, 82300292, and 82302213), National Key Research and Development Program of China (2021YFC2500500), and Natural Science Foundation of Shanghai (21ZR1413500, 20Y11912000, and 20JC1418400). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

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Bhutani V, Varzideh F, Wilson S, Kansakar U, Jankauskas SS, Santulli G. Bhutani V, et al. J Cardiovasc Dev Dis. 2025 May 30;12(6):207. doi: 10.3390/jcdd12060207. J Cardiovasc Dev Dis. 2025. PMID: 40558642 Free PMC article. Review.

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SLAMF7 Restrains Pro-Inflammatory Macrophage Activation to Counteract Doxorubicin-Induced Cardiotoxicity

Affiliations

SLAMF7 Restrains Pro-Inflammatory Macrophage Activation to Counteract Doxorubicin-Induced Cardiotoxicity

Authors

Affiliations

Abstract

Conflict of interest statement

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