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Acute GLP-1 Agonism Induces Arrhythmogenic Electrical Activity in Aged Mice Heart Through Impaired Cellular Na+ and

Yusuf Olgar1, Ayşegül Durak2, Belma Turan2

  • 1Department of Biophysics, Faculty of Medicine, Ankara University, Ankara, Türkiye.

Anatolian Journal of Cardiology
|December 10, 2024
PubMed
Abstract

Insights

Acute glucagon-like peptide-1 receptor agonism (GLP-1RA) can cause heart rhythm problems in elderly mice by affecting ion channels and calcium regulation. This disruption is linked to casein kinase 2 (CK2) hyperphosphorylation.

Area of Science:

  • Cardiology
  • Pharmacology
  • Gerontology

Background:

  • Glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer benefits for type 2 diabetes, obesity, and aging, but their cardiovascular safety is debated.
  • Some GLP-1RAs cause a sustained heart rate increase, with an unclear mechanism, particularly in the short term.
  • Investigating the acute effects of GLP-1R agonism on the electrical activity of aged hearts is crucial.

Purpose of the Study:

  • To examine the short-term effects of acute GLP-1R agonism on the electrical activity of elderly hearts.
  • To elucidate the underlying molecular mechanisms of GLP-1RA-induced cardiac electrical disturbances in aged individuals.

Main Methods:

  • In vivo electrocardiography in adult and aged BALB/c mice.
  • In vitro electrophysiology and biochemical measurements on isolated aged mouse cardiomyocytes.
  • Assessment of ion channel function (K+ and Na+) and calcium handling.

Main Results:

  • A single liraglutide injection induced arrhythmias in aged mice but not in adults.
  • Liraglutide prolonged action potential repolarization in aged cardiomyocytes by suppressing K+ currents and increasing persistent Na+ currents (Late-INa).
  • Liraglutide increased Ca2+ release and induced casein kinase 2 (CK2) hyperphosphorylation, which was reversible with a CK2 inhibitor.

Conclusions:

  • Acute GLP-1R agonism disrupts cardiac electrical signaling and induces arrhythmia in aged mice.
  • CK2 hyperphosphorylation is a key mechanism mediating GLP-1RA-induced cardiac electrical disturbances in the elderly.
  • These findings offer new insights into the cardiovascular effects of GLP-1RAs in aging populations.

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