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March 10, 2026Physiological ResearchOpen Access

Targeting the Toll-Like Receptor 4 Ameliorates Heart Failure in Aged Mice by Inhibiting the Formation of Neutrophil Extracellular Traps

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Key result

Targeting TLR4 with TAK-242 ameliorated heart failure and attenuated myocardial injury in aged mice by inhibiting the formation of neutrophil extracellular traps.

Why the study?

The precise role and underlying mechanisms of TLR4 in HF remain poorly understood.

Does TLR4 inhibition improve cardiac function and reduce inflammation in aged mice with isoproterenol-induced heart failure?

Population

18-month-old male C57BL/6J mice with isoproterenol-induced HF

Comparison

TAK-242 vs DNase I vs GSK484

Design

Animal experimental study

Follow-up

7 consecutive days

Authors

HLH LiuXCX ChenZWZ Wu

Discussion

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Implication

TLR4 targeting in HF remains hypothesis-generating; does not support clinical use and requires human trials.

Structured PICO

Does TLR4 inhibition improve cardiac function and reduce inflammation in aged mice with isoproterenol-induced heart failure?

P
Population
18-month-old male C57BL/6J mice with isoproterenol-induced heart failure treated with TLR4 or NETs inhibitors.
I
Intervention
TLR4 inhibitor TAK-242 (2 mg/kg), deoxyribonuclease I (DNase I, 5 mg/kg), or peptidylarginine deiminase 4 (PAD4) inhibitor GSK484 (4 mg/kg) via daily intraperitoneal injections for 7 consecutive days.
C
Comparator
Equivalent volume of vehicle (administered to control and HF groups).
O
Outcome
Cardiac function parameters including interventricular septal end-diastolic thickness (IVSd), left ventricular end-diastolic diameter (LVEDd), left ventricular end-systolic diameter (LVESd), fractional shortening (FS), and ejection fraction (EF) assessed by echocardiography.surrogate

Main Result

p-value: p=<0.001

Targeting TLR4 ameliorates heart failure and reduces myocardial inflammation in aged mice by inhibiting the formation of neutrophil extracellular traps.

Limitations

  • Further investigation is warranted to elucidate the key molecular events and regulatory mechanisms upstream and downstream of the TLR4 signaling network.

Cite This Study

Liu et al. (2026) studied Heart Failure. TLR4 inhibitor TAK-242 vs. Vehicle was evaluated on Cardiac function and NETs formation (p=<0.001). Targeting TLR4 with TAK-242 ameliorated heart failure and attenuated myocardial injury in aged mice by inhibiting the formation of neutrophil extracellular traps.

synapsesocial.com/papers/6a9fc9eec95c3c4055efd3f9https://doi.org/10.33549/physiolres.935671
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Also Consider

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

  1. 1Predictors of cardiovascular outcome and rehospitalization in elderly patients with heart failure2018 · 21 citations
  2. 2Temporal neutrophil polarization following myocardial infarction2016 · 403 citations
  3. 3Loss of toll-like receptor 4 ameliorates cardiovascular dysfunction in aged mice2021 · 16 citations
  4. 4Toll-like Receptor 4 Differentially Modulates Cardiac Function in Response to Chronic Exposure to High-Fat Diet and Pressure Overload2023 · 5 citations
  5. 5Reticulon 3 deficiency ameliorates post‐myocardial infarction heart failure by alleviating mitochondrial dysfunction and inflammation2024 · 6 citations