Evidence map›Paper›PMID 37499888›Full record

ArticleFree radical biology & medicine2023

Ferroptosis contributes to catecholamine-induced cardiotoxicity and pathological remodeling.

Yi Chen, Xiaoyun Guo, Yachang Zeng, Xiaoliang Mo, Siqi Hong, Hui He, Jing Li, Rachel Steinmetz, Qinghang Liu

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Free radical biology & medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

25 citing papers in PubMed, 29 citations in OpenAlex.

  1. Observational
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 1 institution in 1 country.

Yi ChenDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Xiaoyun GuoDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Yachang ZengDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Xiaoliang MoDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Siqi HongDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Hui HeDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Jing LiDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Rachel SteinmetzDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA.
Qinghang LiuDepartment of Physiology and Biophysics, University of Washington, Seattle, WA, 98195, USA. Electronic address: qcliu@u.washington.edu.
University of Washington · US

Funding

A K63-Ubiquitination Dependent Necroptosis Signaling Network in the HeartR01HL155035 · NHLBI · UNIVERSITY OF WASHINGTON · PI LIU, QINGHANG · 2021 to 2025
$1.9M
The Deubiquitinase CYLD Controls Multiple Cell Death Pathways in the HeartR01HL160767 · NHLBI · UNIVERSITY OF WASHINGTON · PI LIU, QINGHANG · 2022 to 2025
$1.6M
NHLBI NIH HHS R01 HL155035NHLBI NIH HHS R01 HL160767
6 · The paper itself

Abstract

High levels of circulating catecholamines cause cardiac injury, pathological remodeling, and heart failure, but the underlying mechanisms remain elusive. Here we provide both in vitro and in vivo evidence that excessive β-adrenergic stimulation induces ferroptosis in cardiomyocytes, revealing a novel mechanism for catecholamine-induced cardiotoxicity and remodeling. We found that isoproterenol, a synthetic catecholamine, promoted glutathione depletion and glutathione peroxidase 4 (GPX4) degradation in cardiomyocytes, leading to GPX4 inactivation and enhanced lipid peroxidation. Isoproterenol also promoted heme oxygenase 1 (HO-1) expression by downregulating the transcription suppressor BTB and CNC homology 1 (Bach1), leading to increased labile iron accumulation through heme degradation. Moreover, isoproterenol markedly induced the accumulation of free iron and lipid reactive oxygen species (ROS) in the mitochondria, while targeted inhibition of iron overload and ROS accumulation within mitochondria effectively inhibited ferroptosis in cardiomyocytes. Importantly, isoproterenol administration markedly induced ferroptosis in the myocardium in vivo, associated with elevated non-heme iron accumulation driven by HO-1 upregulation. Strikingly, blockade of ferroptosis with ferrostatin-1 or inhibition of HO-1 activity with zinc protoporphyrin (ZnPP) effectively alleviated cardiac necrosis, pathological remodeling, and heart failure induced by isoproterenol administration. Taken together, our results reveal that catecholamine stimulation primarily induces ferroptotic cell death in cardiomyocyte through GPX4 and Bach1-HO-1 dependent signaling pathways. Targeting ferroptosis may represent a novel therapeutic strategy for catecholamine overload-induced myocardial injury and heart failure.

Indexed as

FerroptosisHeart FailureCardiotoxicityCatecholaminesHumansIronIsoproterenolReactive Oxygen SpeciesCatecholaminesIronIsoproterenolReactive Oxygen SpeciesCardiotoxicityCatecholamineFerroptosisGPX4HO-1Mitochondria

Identifiers

PMID37499888
PMCPMC10529955
OpenAlexW4385235314

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.