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Necessity to evaluate PI3K/Akt signalling pathway in proarrhythmia

Martin Ezeani1, Sunday Elom2

  • 1Department of Chemical Pathology, Faculty of Health Science and Technology, College of Health Science, Ebonyi State University, Abakaliki, Ebonyi State, Nigeria.

Open Heart
|December 21, 2017
PubMed

Insights

Drug-induced proarrhythmia, including QT prolongation, is increasing. The PI3K/Akt pathway shows promise for understanding and preventing these dangerous heart rhythm issues.

Area of Science:

  • Cardiovascular Pharmacology
  • Molecular Cardiology
  • Drug Discovery

Background:

  • Rising incidence of drug-induced QT prolongation and torsades de pointes necessitates understanding proarrhythmia mechanisms.
  • Current antiarrhythmic strategies targeting IKr blockade have safety limitations, driving research into alternative pathways.
  • The PI3K/Akt signaling pathway is implicated in cardiac ion channel function and arrhythmogenesis.

Purpose of the Study:

  • To explore the role of the PI3K/Akt signaling pathway in drug-induced proarrhythmia.
  • To investigate the potential of modulating this pathway for developing safer antiarrhythmic and cancer drugs.
  • To highlight the need for improved drug testing methods and a deeper understanding of PI3K/Akt signaling in arrhythmogenesis.

Main Methods:

  • Investigated the effects of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) on ion channel function in cardiomyocytes.
  • Examined the proarrhythmic potential of PI3K inhibitors used in cancer therapy.
  • Reviewed existing literature on PI3K/Akt signaling and its link to arrhythmogenesis.

Main Results:

  • Cardiomyocyte dialysis with PIP3 normalized ion channel alterations and reduced proarrhythmic features.
  • Reduced PI3K/Akt signaling activity is associated with proarrhythmia, while increased activity promotes cell survival.
  • PI3K inhibitors used in cancer treatment have demonstrated proarrhythmic effects.

Conclusions:

  • The PI3K/Akt pathway presents a potential therapeutic target for mitigating drug-induced proarrhythmia.
  • Further research into PI3K/Akt signaling is crucial for developing effective antiarrhythmic drugs and evaluating cancer therapeutics.
  • Enhanced drug testing strategies are needed to assess arrhythmogenic potential related to this pathway.
Keywords:
arrhythmiascardiac remodellingventricular fibrillation

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