Role of acetylation in doxorubicin-induced cardiotoxicity
Daisong Li,
Yanyan Yang,
Shizhong Wang,
Xiangqin He,
Meixin Liu,
Baochen Bai,
Chao Tian,
Ruicong Sun,
Tao Yu,
Xianming Chu
Affiliations
Daisong Li
Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
Yanyan Yang
Department of Immunology, Basic Medicine School, Qingdao University, Qingdao, 266071, China
Shizhong Wang
Department of Cardiovascular Surgery, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
Xiangqin He
Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
Meixin Liu
Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
Baochen Bai
Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
Chao Tian
Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
Ruicong Sun
Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China
Tao Yu
Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Institute for Translational Medicine, The Affiliated Hospital of Qingdao University, Basic Medicine School, Qingdao University, 38 Deng Zhou Road, Qingdao, 266021, China; Corresponding author. Department of Cardiac Ultrasound, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266000, China.
Xianming Chu
Department of Cardiology, The Affiliated Hospital of Qingdao University, Qingdao, 266000, China; Department of Cardiology, The Affiliated Cardiovascular Hospital of Qingdao University, No. 59 Haier Road, Qingdao, 266071, China; Corresponding author. The Affiliated Cardiovascular Hospital of Qingdao University, No. 5 Zhiquan Road, Qingdao, 266071, China.
As a potent chemotherapeutic agent, doxorubicin (DOX) is widely used for the treatment of a variety of cancers However, its clinical utility is limited by dose-dependent cardiotoxicity, and pathogenesis has traditionally been attributed to the formation of reactive oxygen species (ROS). Accordingly, the prevention of DOX-induced cardiotoxicity is an indispensable goal to optimize therapeutic regimens and reduce morbidity. Acetylation is an emerging and important epigenetic modification regulated by histone deacetylases (HDACs) and histone acetyltransferases (HATs). Despite extensive studies of the molecular basis and biological functions of acetylation, the application of acetylation as a therapeutic target for cardiotoxicity is in the initial stage, and further studies are required to clarify the complex acetylation network and improve the clinical management of cardiotoxicity. In this review, we summarize the pivotal functions of HDACs and HATs in DOX-induced oxidative stress, the underlying mechanisms, the contributions of noncoding RNAs (ncRNAs) and exercise-mediated deacetylases to cardiotoxicity. Furthermore, we describe research progress related to several important SIRT activators and HDAC inhibitors with potential clinical value for chemotherapy and cardiotoxicity. Collectively, a comprehensive understanding of specific roles and recent developments of acetylation in doxorubicin-induced cardiotoxicity will provide a basis for improved treatment outcomes in cancer and cardiovascular diseases.
