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June 17, 2025PLoS ONEOpen Access

Epac1 increases myosin regulatory light-chain phosphorylation, energetic cost of contraction, and susceptibility to heart failure

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Why the study?

The study aimed to investigate the contribution of Epac1, a PKA-independent cAMP effector, to the response of cardiac myofilaments to beta-AR stimulation.

Population

Transgenic mice specifically overexpressing Epac1 in the heart and WT mice

Comparison

Epac1TG vs NTG mice and WT mice treated with 8CPT-AM vs control mice

Design

Animal experimental study

Follow-up

1 week

Authors

YOYoshiki OhnukiKSKenji SuitaMIMisao Ishikawa

Discussion

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Member takes

Overview

Epac1 may accelerate HF under β-stimulation; hypothesis-generating for inhibition strategies pending human validation.

Structured PICO

P
Population
Transgenic mice specifically overexpressing Epac1 in the heart (Epac1TG) and wild-type (WT) mice
I
Intervention
Epac1 overexpression or treatment with 8CPT-AM (an Epac-selective cAMP analogue), and chronic β-AR stimulation via isoproterenol infusion (60 mg/kg/day for 1 week)
C
Comparator
Non-transgenic (NTG) or control mice
O
Outcome
Calcium sensitivity of force and ATPase activity, tension cost, myosin regulatory light chain (RLC) phosphorylation, and left ventricular ejection fractionsurrogate

Epac1 activation increases the energetic cost of cardiac contraction and exacerbates the development of heart failure under chronic β-adrenergic stimulation in a mouse model.

Cite This Study

Ohnuki et al. (2025) studied this question.

synapsesocial.com/papers/6a1bcd690a1f7575939cf29ahttps://doi.org/10.1371/journal.pone.0325986
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Also Consider

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

  1. 1Epac1 increases myosin regulatory light-chain phosphorylation, energetic cost of contraction, and susceptibility to heart failure2024
  2. 2The cAMP binding protein Epac regulates cardiac myofilament function2009 · 85 citations
  3. 3Epac1-dependent phospholamban phosphorylation mediates the cardiac response to stresses2014 · 142 citations
  4. 4Depotentiation of intact rat cardiac muscle unmasks an Epac‐dependent increase in myofilament Ca<sup>2+</sup> sensitivity2015 · 13 citations
  5. 5Epac activation, altered calcium homeostasis and ventricular arrhythmogenesis in the murine heart2008 · 80 citations