4.7 Article

Disruption of histamine/H1R-STAT3-SLC7A11 axis exacerbates doxorubicin-induced cardiac ferroptosis

期刊

FREE RADICAL BIOLOGY AND MEDICINE
卷 192, 期 -, 页码 98-114

出版社

ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2022.09.012

关键词

Doxorubicin; Histamine; Histamine receptor; Ferroptosis; DOX-Induced cardiotoxicity

资金

  1. National Natural Science Foundation of China
  2. Basic Research Project of Shanghai Committee of Science and Technology
  3. Laboratory Animal Science Foundation of Shanghai Committee of Science and Technology
  4. [82170258]
  5. [81521001]
  6. [19JC1411400]
  7. [22ZR1446700]
  8. [19140902000]
  9. [201409005000]

向作者/读者索取更多资源

This study reveals the role of the histamine/H1R signaling pathway in doxorubicin-induced cardiotoxicity. Histamine deficiency or H1R antagonism accelerates myocardial ferroptosis and aggravates doxorubicin-induced cardiotoxicity. These findings provide a potential target for the treatment of doxorubicin-induced cardiotoxicity.
Doxorubicin (DOX) is widely used in the treatment of various cancers, increasing the great risk of adverse cardiovascular events, while the clinical intervention effect is not ideal. Histamine has been documented to participate in pathophysiological processes of cardiovascular diseases and inflammation-associated carcino-genesis. However, the potential roles of histamine in antitumor-related cardiotoxicity have not been fully elucidated. In this study, cardiomyocytes (hiPSC-CMs, HL-1 cells) and mice were treated with DOX to establish DOX-induced cardiotoxicity (DIC) models. Histidine decarboxylase knockout mice (HDC-/-) mice and histamine 1 receptor (H1R) antagonist were used to explore the effect of histamine/H1R signaling on DIC. Our results demonstrated that histamine deficiency or pharmaceutical inhibition of H1R accelerated myocardial ferroptosis, which is responsible for the aggravated DIC both in vivo and in vitro, while the supplementation of exogenous histamine reversed these changes. Our data revealed that the dysfunction of histamine/H1R signaling repressed the activation of transducer and activator of transcription 3 (STAT3), accompanying with decreased expression of solute carrier family7member11 (SLC7A11), a major modulator of ferroptosis. Conclusively, the disruption of histamine/H1R axis triggered ferroptosis and exacerbated DIC possibly by modulating STAT3-SLC7A11 pathway. Our findings point to a potential therapeutic target for DIC and provide more consideration on the usage of antihistamine drugs.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据