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February 7, 2025Cardiovascular DiabetologyOpen Access

Roxadustat exerted protective effects against diabetic myocardial injury in mice by reducing oxidative stress through the upregulation of HIF-1α and UCP2 and activation of the PI3K/AKT/Nrf2 pathway.

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Why the study?

Hyperglycemia-induced oxidative stress leads to cardiomyocyte hypoxia and HIF-1α dysregulation, exacerbating diabetic myocardial injury, but the protective effects and mechanisms of the HIF-PHD inhibitor roxadustat (FG-4592) remain to be explored.

Does Roxadustat improve diabetic myocardial injury in preclinical models?

Population

Diabetic myocardial injury mice and high glucose-induced rat cardiomyocyte models

Comparison

FG-4592 pretreatment vs unexposed models

Design

Preclinical animal and cellular experimental study

Key result

Roxadustat exerted protective effects against diabetic myocardial injury in mice by reducing oxidative stress through the upregulation of HIF-1α and UCP2 and activation of the PI3K/AKT/Nrf2 pathway.

Authors

TFTingting FangChina West Normal UniversityCMCongcong MaMinistry of Education of the People's Republic of ChinaBYBing YangMedical Technologies (Czechia)

Discussion

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Overview

Roxadustat may attenuate diabetic myocardial injury via HIF-1α; leaves open clinical translation in humans.

Structured PICO

Does Roxadustat improve diabetic myocardial injury in preclinical models?

P
Population
38 male C57BL/6J mice, aged 6-8 weeks, used to establish a model of type 2 diabetes mellitus combined with myocardial injury.
I
Intervention
Roxadustat (FG-4592) pretreatment
O
Outcome
Changes in oxidative stress, mitochondrial function, and related pathwayssurrogate

Roxadustat protects against diabetic myocardial injury in preclinical models by reducing oxidative stress through the HIF-1α/UCP2 and PI3K/AKT/Nrf2 pathways.

Limitations

  • Preclinical animal and in vitro cell model study, which may not fully translate to human clinical outcomes.

Cite This Study

Fang et al. (2025) studied Diabetic myocardial injury (n=38). Roxadustat (FG-4592) vs. Vehicle (double-distilled water) was evaluated on Myocardial oxidative stress and mitochondrial function. Roxadustat exerted protective effects against diabetic myocardial injury in mice by reducing oxidative stress through the upregulation of HIF-1α and UCP2 and activation of the PI3K/AKT/Nrf2 pathway.

synapsesocial.com/papers/6a8b8e01fe910689a28935f2https://doi.org/10.1186/s12933-025-02601-2
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Antianemia Drug Roxadustat (FG-4592) Protects Against Doxorubicin-Induced Cardiotoxicity by Targeting Antiapoptotic and Antioxidative Pathways2020 · 37 citations
  2. 2Roxadustat Attenuates Adverse Remodeling Following Myocardial Infarction in Mice2024 · 10 citations
  3. 3Activation of the hypoxia-inducible factor pathway by roxadustat improves glucose metabolism in human primary myotubes from men2024 · 4 citations
  4. 4Fucoxanthin protects neonatal rat cardiomyocytes and attenuates high glucose-mediated oxidative stress via the AMPK pathway2020 · 4 citations
  5. 5Combined dapagliflozin and roxadustat effectively protected heart and kidney against cardiorenal syndrome-induced damage in rodent through activation of cell stress-Nfr2/ARE signalings and stabilizing HIF-1α2024 · 7 citations