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MicroRNA-135a regulates sodium-calcium exchanger gene expression and cardiac electrical activity

Eric Duong1, Jiening Xiao2, Xiao Yan Qi2

  • 1Department of Pharmacology and Therapeutics, McGill University, Montreal, Canada; Department of Medicine, Montreal Heart Institute and Université de Montréal, Montreal, Canada.

Heart Rhythm
|February 12, 2017
PubMed
Abstract

Insights

MicroRNA-135a (miR-135a) is downregulated after complete atrioventricular block (CAVB), impacting sodium-calcium exchanger 1 (NCX1) expression. This miR-135a/NCX1 interaction influences cardiomyocyte function and may promote proarrhythmic remodeling.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genetics

Background:

  • Complete atrioventricular block (CAVB) induces cardiac remodeling and increases arrhythmia risk.
  • MicroRNAs (miRNAs) are critical regulators of gene expression involved in cardiac remodeling.

Purpose of the Study:

  • To investigate miRNA expression changes following CAVB.
  • To identify novel miRNAs implicated in CAVB-induced arrhythmogenic cardiac remodeling.

Main Methods:

  • CAVB induced in mice via His-bundle ablation.
  • miRNA expression analyzed using microarrays and qPCR.
  • miRNA targets predicted and validated via luciferase assays.
  • Functional effects studied in neonatal rat ventricular myocytes using overexpression models.

Main Results:

  • miRNA-135a (miR-135a) was significantly downregulated 24 hours post-CAVB.
  • miR-135a was predicted and validated to target the sodium-calcium exchanger type 1 (NCX1).
  • miR-135a overexpression reduced NCX1 expression and altered cardiomyocyte calcium handling and automaticity.

Conclusions:

  • miR-135a negatively regulates NCX1 expression in the heart.
  • Downregulation of miR-135a after CAVB may contribute to proarrhythmic remodeling by affecting NCX1.
  • miR-135a is a potential therapeutic target for CAVB-associated arrhythmias.
Keywords:
Atrioventricular blockMicroRNA, miR-135aNa(+)/Ca(2+) exchangerPosttranscriptional regulation

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