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

JACC Basic Transl Sci

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 Diseas

Published: August 2025


Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12399171PMC
http://dx.doi.org/10.1016/j.jacbts.2025.02.015DOI Listing

Publication Analysis

Top Keywords

doxorubicin-induced cardiotoxicity
8
role slamf7
8
slamf7
7
dic
5
slamf7 restrains
4
restrains pro-inflammatory
4
pro-inflammatory macrophage
4
macrophage activation
4
activation counteract
4
counteract doxorubicin-induced
4

Similar Publications

20-Deoxyingenol attenuated doxorubicin-induced cardiotoxicity by promoting autolysosome degradation through the UCHL3-TFEB pathway.

Phytomedicine

September 2025

Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong, China; Heart Center of Zhujiang Hospital, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Guangzhou, Guangdong, China; Heart

Background: Impaired autophagic flux is an essential contributor to doxorubicin (DOX)-induced cardiotoxicity (DIC). TFEB is recognized as a key regulator of DOX-induced autolysosome accumulation; however, the mechanisms by which DOX suppresses TFEB expression remain unclear. 20-Deoxyingenol (20-DOI) is a small-molecule compound whose potential protective effects against DIC has not yet been elucidated.

View Article and Find Full Text PDF

Small extracellular vesicles orchestrated pathological communications between breast cancer cells and cardiomyocytes as a novel mechanism exacerbating anthracycline cardiotoxicity by fueling ferroptosis.

Redox Biol

September 2025

National Clinical Research Center for Geriatric Diseases, The Second Medical Center, Chinese PLA General Hospital, 100853, Beijing, China; Institute of Geriatric Medicine, The Second Medical Center, Chinese PLA General Hospital, 100853, Beijing, China.

Small extracellular vesicles (sEVs) critically orchestrate inter-tissue and inter-organ communications and may play essential roles in heart-tumor interaction. However, whether cancer-secreted sEVs affect the progression of doxorubicin-induced cardiotoxicity (DOXIC) via orchestrating the tumor cell-cardiomyocyte crosstalk has not yet been explored. Herein, we reveal that Doxorubicin (DOX)-treated breast cancer cells secrete sEVs (D-BCC-sEVs) that exacerbate DOX-induced ferroptosis of human iPSC-derived cardiomyocytes (hiCMs).

View Article and Find Full Text PDF

Doxorubicin (DOX)‑induced cardiotoxicity (DIC) remains a critical challenge in cancer therapy, significantly limiting its use in clinical practice. The underlying mechanisms involve disruptions in cardiac metabolism and mitochondrial dysfunction. The heart relies on mitochondrial oxidative phosphorylation to produce ATP, which is essential for maintaining both contraction and relaxation.

View Article and Find Full Text PDF

Mitochondrial sORF-Encoded Peptide MODICA Protects the Heart From Doxorubicin-Induced Cardiac Injury by Suppressing VDAC Oligomerization.

Circ Heart Fail

September 2025

Department of Cardiology, Center for Translational Medicine, Institute of Precision Medicine, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. (J.W., K.L., Y.Y., X.X., T.X., H.X., H.Z., T.D., Y.L., C.L., X.L., Y.D., J.-S.O., Y.C., Z.-P.H.).

Background: Doxorubicin (DOX) cardiotoxicity increases cardiovascular risk in cancer patients, mainly through mitochondrial damage. However, the underlying mechanisms remain unclear, and whether mitochondrial short open reading frame-encoded peptides can mitigate DOX-induced cardiotoxicity is unknown.

Methods: Five adeno-associated viruses expressing mitochondrial short open reading frame-encoded peptides under the cardiac troponin T promoter, including MODICA (mito-SEP protector against DOX-induced cardiac injury), were screened in a DOX-induced cardiotoxicity mouse model (n=3-5 per group).

View Article and Find Full Text PDF

Background: Doxorubicin (Dox) is a chemotherapy medication used in the therapy of cancers. However, despite its killing of cancer cells, Dox is toxic to the heart and can lead to heart failure. This outcome in turn poses a therapeutic challenge given the limited treatment options available to these individuals.

View Article and Find Full Text PDF