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May 16, 2026Cardiovascular Research

Selective cardiomyocyte loss triggers myocardial regeneration via miR221 driven activation of cardiac stem cells and p57 suppression

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Key result

Ablating ~20% of adult mouse cardiomyocytes triggers complete recovery via miR-221-driven cardiac stem cell activation.

Why the study?

It remained unclear whether the limited regenerative capacity of the adult mammalian heart can be amplified in response to acute cardiomyocyte loss.

Population

Tg-Myh6MCM:R26stop-DTA mice

Design

Preclinical animal study

Follow-up

28 days

Authors

FMF MarinoMagna Graecia UniversityMSM ScaliseMagna Graecia UniversityNSN SalernoMagna Graecia University

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Overview

Warrants caution in tamoxifen-inducible ablation models; leaves open whether adult regeneration can be amplified after acute cardiomyocyte loss.

Key Points

  • This research explores how selective loss of cardiomyocytes can trigger myocardial regeneration and the underlying molecular mechanisms involved.
  • Used Tg-Myh6MCM:R26stop-DTA mice for controlled cardiomyocyte ablation via tamoxifen activation of diphtheria toxin.
  • Implanted osmotic mini-pumps to release BrdU for tracking new cell generation over 28 days.
  • Examined effects of 5-Fluorouracil on proliferating cardiac stem cells to confirm their necessity for regeneration.
  • Diphtheria toxin activation led to approximately 20% loss of ventricular cardiomyocytes and subsequent systolic dysfunction.
  • Surviving mice showed complete recovery within 28 days, with levels of new cardiomyocytes matching initial loss rates.
  • Cardiac stem cells were activated through miR-221 induced repression of p57, demonstrating their critical role in regeneration.

Structured PICO

P
Population
Tg-Myh6MCM:R26stop-DTA mice
I
Intervention
Tamoxifen-induced controlled, cardiomyocyte-restricted ablation via Diphtheria Toxin A (DTA) activation
O
Outcome
Anatomical and functional recovery and cardiomyocyte renewalsurrogate

This preclinical study demonstrates that the adult mammalian heart can regenerate up to 20% of its ventricular cardiomyocytes within one month following selective ablation, mediated by endogenous cardiac stem cells and a miR-221/p57 axis.

Cite This Study

Marino et al. (2026) studied Cardiomyocyte loss. Tamoxifen-induced Diphtheria Toxin A (DTA) activation was evaluated on Cardiomyocyte loss and anatomical/functional recovery. Selective genetic ablation of ~20% of ventricular cardiomyocytes in adult mice triggered complete anatomical and functional recovery within 28 days via miR-221-driven cardiac stem cell activation.

synapsesocial.com/papers/6a080af2a487c87a6a40cf65https://doi.org/10.1093/cvr/cvag092.012
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Also Consider

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

  1. 1Granulocyte colony-stimulating factor treatment plus dipeptidylpeptidase-IV inhibition augments myocardial regeneration in mice expressing cyclin D2 in adult cardiomyocytes2011 · 33 citations
  2. 2Inhibition of Senescence‐Associated Genes Rb1 and Meis2 in Adult Cardiomyocytes Results in Cell Cycle Reentry and Cardiac Repair Post–Myocardial Infarction2019 · 73 citations
  3. 3Abstract Thu014: Checkpoint kinase-2 regulates cardiomyocyte cell cycle and ameliorates cardiac function after myocardial infarction2025
  4. 4Ablation of endogenously cycling adult cardiomyocytes worsens myocardial function after injury2020 · 1 citations
  5. 5Abstract Thu031: MCM2 overexpression in the adult heart promotes cardiac rejuvenation and protection after infarction.2025