Developmental aspects of cardiac arrhythmogenesis

Cardiovasc Res. 2011 Jul 15;91(2):243-51. doi: 10.1093/cvr/cvr134. Epub 2011 May 12.

Abstract

The transcriptional regulation orchestrating the development of the heart is increasingly recognized to play an essential role in the regulation of ion channel and gap junction gene expression and consequently the proper generation and conduction of the cardiac electrical impulse. This has led to the realization that in some instances, abnormal cardiac electrical function and arrhythmias in the postnatal heart may stem from a developmental abnormality causing maintained (epigenetic) changes in gene regulation. The role of developmental genes in the regulation of cardiac electrical function is further underscored by recent genome-wide association studies that provide strong evidence that common genetic variation, at loci harbouring these genes, modulates electrocardiographic indices of conduction and repolarization and susceptibility to arrhythmia. Here we discuss recent findings and provide background insight into these complex mechanisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arrhythmias, Cardiac / embryology
  • Arrhythmias, Cardiac / genetics*
  • Arrhythmias, Cardiac / metabolism
  • Arrhythmias, Cardiac / physiopathology
  • Gene Expression Regulation, Developmental*
  • Genetic Predisposition to Disease
  • Heart Conduction System / embryology
  • Heart Conduction System / metabolism*
  • Heart Conduction System / physiopathology
  • Homeobox Protein Nkx-2.5
  • Homeobox Protein PITX2
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Humans
  • Ion Channels / genetics*
  • Ion Channels / metabolism
  • Phenotype
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism

Substances

  • Homeobox Protein Nkx-2.5
  • Homeodomain Proteins
  • IRX5 protein, human
  • Ion Channels
  • NKX2-5 protein, human
  • T-Box Domain Proteins
  • T-box transcription factor 5
  • Transcription Factors