Translational Proteomics Analysis of Anthracycline-Induced Cardiotoxicity From Cardiac Microtissues to Human Heart Biopsies
Abstract
Anthracyclines, including doxorubicin, idarubicin, and epirubicin, are common antitumor drugs as well as well-known cardiotoxic agents. This study analyzed the proteomics alteration in cardiac tissues caused by these 3 anthracyclines analogs. The in vitro human cardiac microtissues were exposed to drugs in 2 weeks; the proteomic data were measured at 7 time points. The heart biopsy data were collected from heart failure patients, in which some patients underwent anthracycline treatment. The anthracyclines-affected proteins were separately identified in the in vitro and in vivo dataset using the WGCNA method. These proteins engage in different cellular pathways including translation, metabolism, mitochondrial function, muscle contraction, and signaling pathways. From proteins detected in 2 datasets, a protein-protein network was established with 4 hub proteins, and 7 weighted proteins from both cardiac microtissue and human biopsies data. These 11 proteins, which involve in mitochondrial functions and the NF-κB signaling pathway, could provide insights into the anthracycline toxic mechanism. Some of them, such as HSPA5, BAG3, and SH3BGRL, are cardiac therapy targets or cardiotoxicity biomarkers. Other proteins, such as ATP5F1B and EEF1D, showed similar responses in both the in vitro and in vivo data. This suggests that the in vitro outcomes could link to clinical phenomena in proteomic analysis. Show more
Permanent link
https://doi.org/10.3929/ethz-b-000493856Publication status
publishedExternal links
Journal / series
Frontiers in GeneticsVolume
Pages / Article No.
Publisher
Frontiers MediaSubject
WGCNA; Cardiotoxicity; Anthracyclines; Proteomics; Drug side-effectOrganisational unit
02207 - Functional Genomics Center Zurich / Functional Genomics Center Zurich
08828 - Schlapbach, Ralph (Tit.-Prof.)
Funding
602156 - Hepatic and Cardiac Toxicity Systems modelling (EC)
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