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January 13, 2021Scientific ReportsOpen Access

Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway

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Key result

Fenofibrate attenuated doxorubicin-induced cardiac dysfunction and significantly increased circulating endothelial progenitor cells (2% vs 0.5% of total events) in mice.

Why the study?

EPCs restore endothelial function in heart failure, prompting investigation into whether fenofibrate improves myocardial function via eNOS-mediated EPC activation in doxorubicin-induced cardiomyopathy.

Does fenofibrate improve myocardial function in a doxorubicin-induced cardiomyopathy mouse model?

Population

Wild-type mice with doxorubicin-induced cardiomyopathy

Comparison

Vehicle vs DOX + saline vs DOX + fenofibrate vs DOX + fenofibrate + L-NAME

Design

Animal experimental study

Follow-up

4 weeks

Authors

WHWen‐Pin HuangWYWei-Hsian YinJCJia-Shiong Chen

Discussion

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Member takes

Overview

Fenofibrate increases EPCs in DOX cardiomyopathy mice; leaves open clinical translation to human HF endothelial repair.

Structured PICO

Does fenofibrate improve myocardial function in a doxorubicin-induced cardiomyopathy mouse model?

P
Population
53 male FVB/NJ mice, 8 weeks of age, subjected to doxorubicin-induced cardiomyopathy and treated with fenofibrate for 4 weeks.
I
Intervention
Fenofibrate
C
Comparator
Vehicle, DOX + saline
O
Outcome
DOX-induced cardiac atrophy, myocardial dysfunction, number of circulating EPCs, and tissue inflammationsurrogate

Main Result

Absolute Event Rate: 2% vs 0.5%

p-value: p=<0.05

Fenofibrate ameliorates doxorubicin-induced cardiac toxicity in mice by promoting Akt/eNOS and VEGF to activate EPC pathways.

Limitations

  • Could not rule out the involvement of the AMPK activation pathway in the protective effects of fenofibrate.
  • Lack of allogeneic EPCs to serve as control samples to directly prove the hypothesis.

Cite This Study

Huang et al. (2021) studied Doxorubicin-induced cardiomyopathy (n=53). Fenofibrate vs. Saline was evaluated on Circulating endothelial progenitor cells (EPCs) as a percentage of total events (p=<0.05). Fenofibrate attenuated doxorubicin-induced cardiac dysfunction and significantly increased circulating endothelial progenitor cells (2% vs 0.5% of total events) in mice.

synapsesocial.com/papers/6a33030f7282da616280759fhttps://doi.org/10.1038/s41598-021-80984-4
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Also Consider

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

  1. 1Endothelin-1-Induced Cell Hypertrophy in Cardiomyocytes is Improved by Fenofibrate: Possible Roles of Adiponectin2016 · 23 citations
  2. 2Erythropoietin improves myocardial performance in doxorubicin-induced cardiomyopathy2006 · 77 citations
  3. 3Cardioprotective effects of fish omega-3 fatty acids on doxorubicin-induced cardiotoxicity in rats2013 · 39 citations
  4. 4CD34 <sup>+</sup> and Endothelial Progenitor Cells in Patients With Various Degrees of Congestive Heart Failure2004 · 374 citations
  5. 5Doxorubicin induced heart failure: Phenotype and molecular mechanisms2015 · 319 citations