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Interactions between the ERK1/2 signaling pathway and PCAF play a key role in PE‑induced cardiomyocyte hypertrophy

Qian Mao1, Shuqi Wu1, Chang Peng1

  • 1Department of Pediatrics, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, P.R. China.

Molecular Medicine Reports
|July 19, 2021
PubMed

Insights

Phenylephrine (PE) induces cardiomyocyte hypertrophy via extracellular signal-regulated kinase (ERK)1/2 signaling, which interacts with PCAF to modify histone acetylation. Inhibiting ERK or histone acetylase prevents hypertrophy.

Area of Science:

  • Cardiovascular Biology
  • Epigenetics
  • Molecular Cardiology

Background:

  • Cardiomyocyte hypertrophy is a key factor in chronic heart failure.
  • Extracellular signal-regulated protein kinase (ERK) signaling is crucial for cardiomyocyte hypertrophy.
  • Previous studies linked phenylephrine (PE)-induced hypertrophy to histone H3K9ac hyperacetylation by PCAF, but upstream pathways remained unclear.

Purpose of the Study:

  • To investigate the role of the ERK1/2 signaling pathway in PE-induced cardiomyocyte hypertrophy.
  • To elucidate the interaction between ERK1/2, PCAF, and histone H3K9ac acetylation in this process.

Main Methods:

  • Established a mouse cardiomyocyte hypertrophy model using PE treatment in vitro.
  • Utilized an ERK inhibitor (U0126) and a histone acetylase inhibitor (anacardic acid; AA).
  • Assessed the interaction of phospho-ERK1/2 with PCAF and changes in H3K9ac acetylation patterns.

Main Results:

  • Phospho-ERK1/2 was found to interact with PCAF, altering H3K9ac acetylation.
  • U0126 and/or AA treatment attenuated phospho-ERK1/2 and H3K9ac overexpression by inhibiting PCAF expression.
  • Inhibitors reduced the expression of cardiac hypertrophy biomarker genes and prevented hypertrophy.

Conclusions:

  • Revealed a novel mechanism where anacardic acid protects against PE-induced cardiomyocyte hypertrophy via the ERK1/2 pathway and H3K9ac modification.
  • Findings suggest potential therapeutic strategies for hypertrophic cardiomyopathy by targeting ERK1/2 and histone acetylation.

Keywords:
ERK‑signaling pathwayanacardic acidcardiomyocyte hypertrophyhistone acetylation

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