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Enhancing the Engraftment of Human Induced Pluripotent Stem Cell-derived Cardiomyocytes via a Transient Inhibition of Rho Kinase Activity
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PLK1 Downregulation Attenuates ET-1-Induced Cardiomyocyte Hypertrophy by Suppressing the ERK1/2 Pathway

Jie Ding1, Anqi Yang1, Liping Zhou1

  • 1Department of Cardiology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, 200120, China.

Journal of Cardiovascular Translational Research
|March 17, 2025
PubMed

Insights

Polo-like kinase 1 (PLK1) drives cardiomyocyte hypertrophy, a key factor in heart failure development. Inhibiting PLK1 reduces cardiac cell enlargement and markers, offering potential therapeutic strategies for heart disease.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Cell Biology

Background:

  • Cardiomyocyte hypertrophy is a significant risk factor for heart failure.
  • The precise molecular mechanisms underlying cardiomyocyte hypertrophy remain incompletely understood.

Purpose of the Study:

  • To investigate the role of Polo-like kinase 1 (PLK1) in endothelin-1 (ET-1)-induced cardiomyocyte hypertrophy.
  • To elucidate the molecular pathways involved in PLK1-mediated cardiac hypertrophy.

Main Methods:

  • Assessed PLK1 expression in hypertrophic cardiomyocytes and cardiac tissue.
  • Utilized Plk1 knockdown and a PLK1 inhibitor (BI2536) to evaluate effects on cardiomyocyte size and hypertrophic markers (ANP, BNP, β-MHC).
  • Investigated the involvement of the ERK1/2 signaling pathway and tested PLK1 deficiency in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

Main Results:

  • PLK1 expression was significantly increased in ET-1-induced and pressure overload-induced cardiac hypertrophy.
  • Plk1 knockdown and PLK1 inhibition reduced cardiomyocyte size and suppressed hypertrophic marker expression.
  • The ERK1/2 pathway was identified as a critical downstream mediator of PLK1's effects.
  • PLK1 deficiency attenuated hypertrophy in hiPSC-CMs.

Conclusions:

  • PLK1 plays a crucial role in regulating ET-1-induced cardiomyocyte hypertrophy.
  • The ERK1/2 pathway mediates the hypertrophic effects of PLK1.
  • PLK1 represents a potential therapeutic target for pathological cardiac hypertrophy.

Keywords:
Cardiomyocyte HypertrophyERK1/2Endothelin-1PLK1hiPSC-CMs

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