SLAMF7抑制促炎巨噬细胞活化以对抗阿霉素诱导的心脏毒性。

IF 8.4 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS

JACC: Basic to Translational Science Pub Date : 2025-04-16 DOI:10.1016/j.jacbts.2025.02.015

Ao Liu, Peiyuan Bai, Hongmin You, Zehao Zhuang, Fangyan Tian, Haobo Weng, Xuemei Wei, Lu Tang, Litao Wang, Chaobao Liu, Jinghong Zhang, Minmin Sun, Shuning Zhang, Xianhong Shu, Junbo Ge

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引用次数: 0

摘要

阿霉素诱导的心脏毒性（DIC）对癌症治疗提出了重大挑战。本研究探讨了SLAMF7在DIC中的作用，特别是在巨噬细胞介导的炎症中。使用SLAMF7敲除小鼠，我们发现SLAMF7缺乏会加剧DIC并放大炎症反应。在机制上，SLAMF7与TNF受体相关因子6相互作用，减弱核因子κB信号，减少氧化应激和促炎细胞因子。值得注意的是，给药重组SLAMF7蛋白可有效缓解DIC。这些发现强调了SLAMF7在预防DIC中的关键作用，将其定位为一个有希望的治疗靶点。

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

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.

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来源期刊

JACC: Basic to Translational Science CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

14.20

自引率

1.00%

发文量

161

审稿时长

16 weeks

期刊介绍： JACC: Basic to Translational Science is an open access journal that is part of the renowned Journal of the American College of Cardiology (JACC). It focuses on advancing the field of Translational Cardiovascular Medicine and aims to accelerate the translation of new scientific discoveries into therapies that improve outcomes for patients with or at risk for Cardiovascular Disease. The journal covers thematic areas such as pre-clinical research, clinical trials, personalized medicine, novel drugs, devices, and biologics, proteomics, genomics, and metabolomics, as well as early phase clinical trial methodology.