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Altered expression of hyperpolarization-activated cyclic nucleotide-gated channels and microRNA-1 and -133 in

Yao-Dong Li1, Yi-Fan Hong1, Yueerguli Yusufuaji1

  • 1Department of Cardiology, The First Affiliated Hospital, Xinjiang Medical University, Urumqi, Xinjiang Uyghur 830011, P.R. China.

Molecular Medicine Reports
|May 26, 2015
PubMed

Insights

Age-associated atrial fibrillation is linked to increased HCN2 and HCN4 channel expression and decreased miR-1 and miR-133 levels in the atrium. These changes in hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and microRNAs may trigger arrhythmias.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Geroscience

Background:

  • Hyperpolarization-activated cyclic nucleotide-gated (HCN) cation channels are crucial for pacemaker currents in the atrium.
  • MicroRNA (miR) families miR-1 and miR-133 are known regulators of myocardial function, including HCN channel expression.

Purpose of the Study:

  • To investigate the hypothesis that age-dependent alterations in HCN2, HCN4, miR-1, and miR-133 expression contribute to age-associated atrial fibrillation.
  • To determine the correlation between the expression levels of these molecules in adult and aged patients with and without atrial fibrillation.

Main Methods:

  • Analysis of right atrial appendage samples from 60 patients undergoing coronary artery bypass grafting.
  • Quantification of target RNA and protein expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot.

Main Results:

  • Aged patients with atrial fibrillation showed significantly higher HCN2 and HCN4 mRNA and protein levels, and significantly lower miR-1 and miR-133 levels compared to aged patients with sinus rhythm.
  • Aged patients with sinus rhythm exhibited significantly higher HCN2 and HCN4 mRNA and protein levels, and significantly lower miR-1 and miR-133 levels compared to adult patients with sinus rhythm.
  • HCN2 and HCN4 expression levels increased with age, with a more pronounced increase observed in patients with age-associated atrial fibrillation.

Conclusions:

  • Age-dependent changes in HCN2, HCN4, miR-1, and miR-133 expression are associated with atrial fibrillation in the elderly.
  • These molecular and electrophysiological alterations may promote ectopic beats, potentially triggering atrial fibrillation.

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