What question did this study set out to answer?

To investigate whether exercise protects against doxorubicin-induced cardiotoxicity by regulating B cell activation, antibody secretion, and inhibitory receptor signaling.

February 7, 2024Circulation ResearchOpen Access

Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells

Q: What is the clinical evidence from this study?

Study design: Other. Population: Doxorubicin-induced cardiotoxicity. Intervention: Treadmill running exercise vs. No exercise / control. Primary outcome: Cardiac function, apoptosis, atrophy, fibrosis, and antibody deposition.

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Key result

Exercise training protected against doxorubicin-induced cardiotoxicity in mice by upregulating Fc gamma receptor IIB expression in B cells, reducing cardiac apoptosis and fibrosis.

Why the study?

Although exercise training protects against doxorubicin-induced cardiotoxicity, the involvement of immune cells remains unclear.

Does treadmill running exercise prevent doxorubicin-induced cardiotoxicity in mice via B cell regulation?

Population

Mice administered with doxorubicin (5 mg/kg per week, 20 mg/kg cumulative dose)

Comparison

Treadmill running exercise and adoptive transfer of exercise-derived B cells vs controls

Design

Animal and in vitro preclinical mechanistic study

Authors

JWJing WangSecond Affiliated Hospital of Jilin University SLShuqin LiuShanghai University XMXinxiu MengShanghai University

Discussion

Member takes

Implication

Does not support exercise for doxorubicin cardiotoxicity prevention in patients; leaves open FcγRIIB-mediated B-cell mechanisms in future models.

Key Points

To investigate whether exercise protects against doxorubicin-induced cardiotoxicity by regulating B cell activation, antibody secretion, and inhibitory receptor signaling.
Mice received treadmill running exercise during weekly doxorubicin administration (5 mg/kg per week, cumulative dose 20 mg/kg).
Splenic B cells from exercised wild-type or Fc gamma receptor IIB-deficient donor mice were adoptively transferred into B cell-deficient (μMT−/−) recipient mice, supplemented by in vitro coculture assays.
Exercise training improved cardiac function and reduced cardiac apoptosis, atrophy, fibrosis, antibody deposition, and proinflammatory signaling in doxorubicin-treated mice.
Pharmacological or genetic depletion of B cells phenocopied the cardioprotective effects of exercise, and adoptive transfer of exercised B cells restored protection in μMT−/− mice.
Cardioprotection was eliminated when transferring B cells lacking Fc gamma receptor IIB, demonstrating that exercise upregulates this inhibitory receptor to elevate the activation threshold of B cells.

Structured PICO

Does treadmill running exercise prevent doxorubicin-induced cardiotoxicity in mice via B cell regulation?

Population

Mice administered with doxorubicin to induce cardiotoxicity.

Intervention

Treadmill running exercise; adoptive transfer of exercise-derived splenic B cells.

Comparator

Control (non-exercised) mice and control B cells.

Outcome

Doxorubicin-induced cardiotoxicity (assessed via cardiac function, cardiac apoptosis, atrophy, fibrosis, cardiac antibody deposition, and proinflammatory responses).surrogate

Exercise mitigates doxorubicin-induced cardiotoxicity in mice by upregulating Fc gamma receptor IIB in B cells, revealing a novel immunomodulatory mechanism of exercise-induced cardioprotection.

Cite This Study

Wang et al. (2024) studied Doxorubicin-induced cardiotoxicity. Treadmill running exercise vs. No exercise / control was evaluated on Cardiac function, apoptosis, atrophy, fibrosis, and antibody deposition. Exercise training protected against doxorubicin-induced cardiotoxicity in mice by upregulating Fc gamma receptor IIB expression in B cells, reducing cardiac apoptosis and fibrosis.

synapsesocial.com/papers/6a83083028b8a62be998fde0 https://doi.org/10.1161/circresaha.123.323346

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Implication

Does not support exercise for doxorubicin cardiotoxicity prevention in patients; leaves open FcγRIIB-mediated B-cell mechanisms in future models.

Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Exercise Inhibits Doxorubicin-Induced Cardiotoxicity via Regulating B Cells

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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