Abstract
Human congestive heart failure is accompanied by structural and electrical alterations leading to the development of an arrhythmogenic substrate. This substrate is associated with the “sudden cardiac death” due to ventricular tachycardia or ventricular fibrillation. Multiple studies link distinct transcription factors to the transcriptional regulation of genes related to the formation of an arrhythmogenic substrate. In addition to cardiac hypertrophy the up- or downregulation of ion channels, calcium-handling proteins, and proteins forming gap junctions play a pivotal role in the progression of heart failure. This review summarizes the transcriptional regulation of selected genes implicated in the formation of an arrhythmogenic substrate. In this context we provide an overview of relevant transcription factors, activating stimuli and pathways, the evidence of binding to respective elements in the promoter of target genes and the associated mRNA regulation in animal models. Finally, possible therapeutic consequences are discussed.
Keywords: Arrhythmogenic substrate, cardiac remodeling, gene regulation, human heart failure, hypertrophic response, transcription factors.
Current Medicinal Chemistry
Title:The Role of Transcription Factors in the Formation of an Arrhythmogenic Substrate in Congestive Human Heart Failure
Volume: 21 Issue: 11
Author(s): J.S. Schulte, M.D. Seidl and F.U. Muller
Affiliation:
Keywords: Arrhythmogenic substrate, cardiac remodeling, gene regulation, human heart failure, hypertrophic response, transcription factors.
Abstract: Human congestive heart failure is accompanied by structural and electrical alterations leading to the development of an arrhythmogenic substrate. This substrate is associated with the “sudden cardiac death” due to ventricular tachycardia or ventricular fibrillation. Multiple studies link distinct transcription factors to the transcriptional regulation of genes related to the formation of an arrhythmogenic substrate. In addition to cardiac hypertrophy the up- or downregulation of ion channels, calcium-handling proteins, and proteins forming gap junctions play a pivotal role in the progression of heart failure. This review summarizes the transcriptional regulation of selected genes implicated in the formation of an arrhythmogenic substrate. In this context we provide an overview of relevant transcription factors, activating stimuli and pathways, the evidence of binding to respective elements in the promoter of target genes and the associated mRNA regulation in animal models. Finally, possible therapeutic consequences are discussed.
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Schulte J.S., Seidl M.D. and Muller F.U., The Role of Transcription Factors in the Formation of an Arrhythmogenic Substrate in Congestive Human Heart Failure, Current Medicinal Chemistry 2014; 21 (11) . https://dx.doi.org/10.2174/09298673113209990172
DOI https://dx.doi.org/10.2174/09298673113209990172 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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