ATNFAIP8--dependent survival axis protects cardiomyocytes from anthracycline-induced cardiotoxicity
Clicks: 8
ID: 323418
2026
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This
article has not been analysed, so there is no overall score —
reader engagement is measured and shown alongside.
Reader Engagement
Steady Performance
2.1
/100
8 views
7 readers
AI Quality Assessment
Not analyzed
Readership in this journal
SteadyRanked #214 of 291 articles by views in European heart journal supplements : journal of the European Society of Cardiology
Most read
Least read
Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 291 in total.
Mint this article as an NFT
Not yet mintedCreate a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.
5
SUSD
one-off · no wallet required
Abstract
Abstract Background Anthracycline-induced cardiotoxicity limits the therapeutic efficacy of cancer treatment and is characterized by mitochondrial dysfunction, oxidative stress, inflammatory activation, and cardiomyocyte apoptosis. The cardiomyocyte-intrinsic survival mechanisms that counteract these stress pathways remain incompletely defined. Methods Doxorubicin-induced cardiotoxicity was modeled using human induced pluripotent stem cell–derived cardiomyocytes and a murine model of anthracycline injury. Cardiomyocyte viability, mitochondrial structure and bioenergetics, oxidative stress, inflammatory signaling, and contractile function were assessed using high-content imaging, ultrastructural analysis, metabolic flux measurements, and functional assays. Transcriptomic profiling was performed to identify candidate survival regulators, followed by molecular, genetic, and functional validation in vitro and in vivo. Results Doxorubicin induced dose-dependent cardiomyocyte injury marked by reduced cell survival, increased apoptosis, mitochondrial ultrastructural disruption, impaired oxidative phosphorylation, excessive reactive oxygen species generation, and increased tumor necrosis factor–α secretion. In vivo, doxorubicin exposure resulted in reduced survival and progressive systolic and diastolic dysfunction accompanied by myocardial architectural disorganization and cardiomyocyte loss. Transcriptomic analysis identified TNFAIP8 as a doxorubicin-responsive gene whose expression was reduced in injured cardiomyocytes and myocardium. Loss of TNFAIP8 was sufficient to impair cardiomyocyte viability and phenocopied key features of doxorubicin-induced injury. Conversely, preservation of TNFAIP8 expression was associated with attenuation of oxidative stress–driven inflammatory signaling, reduced FGFR1 activation, and suppression of caspase-3–dependent apoptosis, accompanied by improved cardiomyocyte survival and contractile performance. Conclusions Doxorubicin-induced cardiotoxicity is driven by oxidative stress–associated inflammatory signaling that converges on destabilization of the cardiomyocyte survival factor TNFAIP8, thereby lowering the apoptotic threshold. Maintenance of TNFAIP8 defines a cardiomyocyte-intrinsic survival axis that preserves mitochondrial integrity, limits apoptotic activation, and protects cardiac structure and function under anthracycline stress.
| Reference Key |
openalex_W7172282616
Use this key to autocite in the manuscript while using
SciMatic Manuscript Manager or Thesis Manager
|
|---|---|
| Authors | Y Liu, S Wang, Y Hsu |
| Journal | European heart journal supplements : journal of the European Society of Cardiology |
| Year | 2026 |
| DOI |
10.1093/eurheartjsupp/suag097.217
|
| URL | |
| Keywords | Keywords not found |
Citations
No citations found. To add a citation, contact the admin at info@scimatic.org
Comments
No comments yet. Be the first to comment on this article.