94% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
ORIGINAL RESEARCH article
Front. Cardiovasc. Med.
Sec. Cardio-Oncology
Volume 12 - 2025 | doi: 10.3389/fcvm.2025.1557119
This article is part of the Research Topic Targets in Cardio-Oncology: Drug Effects and Mechanisms of Action View all 7 articles
The Role of HDAC2 Inhibition in Cardioprotection Against Doxorubicin-Induced Myocardial Injury
Provisionally accepted- 1 Department of Cardiology, China-Japan Union Hospital of Jilin University, Changchun, Jilin Province, China
- 2 Department of Pharmacology, School of Pharmaceutical Sciences, Jilin University, Changchun, Jilin Province, China
- 3 Department of Andrology, the First Hospital of Jilin University, Changchun, China
- 4 Jilin University, Changchun, China
The molecular mechanisms underlying cardioprotection against doxorubicin (DOX)induced myocardial injury are poorly understood. Histone deacetylase 2 (HDAC2) plays a significant role in oxidative stress, apoptosis, and mitochondrial dysfunction and is implicated in many human diseases, This study investigated the relationship between HDAC2 expression and DOX-induced myocardial injury using the in vivo rat model of DOX-induced cardiotoxicity and in vitro experiments with the H9c2 cardiomyocytes. Methods: The rat model of DOX-induced myocardial injury was established by administering DOX via intraperitoneal injections. HDAC2 expression was suppressed by administering rats with sodium butyrate (SB) via intraperitoneal injections. Echocardiography measurements were performed at baseline and on day 15 post-treatment. The rats were euthanized on day 15 and cardiac tissues were harvested. The cardiac tissue samples were analyzed by hematoxylin and eosin H&E staining, immunohistochemistry, Masson staining, Sirius Red staining, TUNEL staining, and western blotting to determine the status of HDAC2 expression and myocardial apoptosis. In the vitro experiments, H9c2 cells were treated with DOX. HDAC2 expression was suppressed using sodium butyrate or transfected cells with the shRNA knockdown HDAC2 (shHDAC2) . The H9c2 cells from different groups were analyzed by Rt-qPCR, CCK-8 cell viability assay, and western blotting to determine the status of HDAC2 expression and cardiomyocyte apoptosis. Results: DOX treatment induced cardiac dysfunction in rats. The cardiac tissues of the DOX-treated rats and H9c2 cells showed significantly higher levels of HDAC2 compared to the corresponding controls. However, inhibition of HDAC2 significantly mitigated DOX-induced myocardial injury in rats. This suggested a strong association between HDAC2 expression and DOX-induced myocardial injury. In the H9c2 cells, HDAC2 knockdown by shHDAC2 alleviated DOX-induced apoptosis by enhacing AKT phosphorylation. These findings demonstrated that HDAC2 silencing protected against DOX-induced cardiomyocyte apoptosis by activating the PI3K/AKT signaling pathway.Suppressing HDAC2 protected against DOX-induced cardiomyocyte apoptosis by activating the PI3K/AKT signaling pathway. Therefore, HDAC2 is a promising therapeutic target for mitigating DOXinduced myocardial injury.
Keywords: HDAC2, Doxorubicin, cardiac function, PI3K/AKT, Apoptosis
Received: 08 Jan 2025; Accepted: 10 Feb 2025.
Copyright: © 2025 Liu, fu, Wang, Liang and Meng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zuowen Liang, Department of Andrology, the First Hospital of Jilin University, Changchun, China
Fanbo Meng, Jilin University, Changchun, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.