Expression of hyperpolarization-activated cyclic nucleotide-gated cation channel (HCN4) is increased in hypertrophic

Huang Wei-qing1, Kong Qing-nuan, Xu Lin

  • 1Department of Pathology, Qingdao Municipal Hospital, Qingdao 266071, Shandong, China.

Insights

Hypertrophic cardiomyopathy (HCM) hearts show significantly higher HCN4 mRNA levels compared to healthy hearts. This suggests increased HCN4 gene expression may contribute to fatal ventricular arrhythmias in HCM patients.

Area of Science:

  • Cardiology
  • Molecular Biology
  • Genetics

Background:

  • Hypertrophic cardiomyopathy (HCM) is a myocardial disease with unknown causes, often leading to sudden cardiac death due to arrhythmia.
  • The hyperpolarization-activated current I(f) is altered in hypertrophic hearts and implicated in arrhythmias.
  • I(f) channels are formed by HCN1-4 subunits; previous studies indicated elevated HCN2 and HCN4 mRNA in rat hypertrophic hearts.

Purpose of the Study:

  • To investigate HCN gene expression in human hypertrophic cardiomyopathy (HCM) myocardium.
  • To determine if HCN4 mRNA levels are altered in human HCM hearts compared to healthy controls.

Main Methods:

  • Left ventricular tissue samples were obtained from four HCM patients and six healthy individuals.
  • Fluorescent quantitative reverse transcription-polymerase chain reaction (RT-PCR) was employed to quantify HCN4 mRNA expression levels.

Main Results:

  • HCM hearts exhibited myofiber disorganization and interstitial fibrosis, absent in controls.
  • Quantitative PCR revealed significantly higher mean HCN4 mRNA copy numbers in HCM hearts (2.2×10^7) compared to control hearts (8.17×10^3).

Conclusions:

  • Elevated HCN4 mRNA levels in human HCM hearts were observed.
  • Up-regulation of HCN4 gene expression is suggested as a potential mechanism contributing to ventricular arrhythmia and sudden death in HCM.
Abstract

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